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Stem cell treatment.

The new frontier and medical innovation in recovery and health.

The Future of Stem Cell Treatments for various human ailments.

 

Acute Myocardial Infarction (AMI)

  1. Brief description of the condition:
    AMI is a serious medical condition that occurs when blood flow to the heart is suddenly blocked, causing damage to the heart muscle.
  2. Technical justification for the use of the cells:
    MSCs have regenerative and anti-inflammatory properties that can help repair damaged heart tissue and improve cardiac function.
  3. Specifications:
    • Cell source: MSCs derived from bone marrow or adipose tissue are generally used.PMC+33BioMed Central+33PMC+33
    • Handling details for the procedure: Cells are isolated, expanded in culture and administered by intracoronary or intravenous injection.
    • Dosage: Varies by clinical trial; commonly 10^6 to 10^8 cells per infusion.
    • Contraindications: No specific contraindications have been established, but caution is recommended in patients with a history of malignant neoplasms.
    • Detected adverse effects: Studies have reported that MSCs are generally safe, with few serious adverse events related to therapy.
  • Bibliographic references:
    • Miao, C., Lei, M., Hu, W., Han, S., Wang, Q., & Aung, L. H. H. (2015). Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease. International Journal of Molecular Sciences, 16(8), 17955-17980. https://doi.org/10.3390/ijms160817955.​

Knee Osteoarthritis

  1. Brief description of the condition:
    Osteoarthritis is a degenerative joint disease that causes pain, swelling and decreased mobility, commonly affecting the knee.
  2. Technical justification for the use of the cells:
    MSCs can differentiate into chondrocytes and have anti-inflammatory effects, which may contribute to cartilage regeneration and symptom relief.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow, adipose tissue or umbilical cord.
    • Management details for the procedure: The cells are isolated, expanded and administered by intra-articular injection into the affected knee.
    • Dosage: Doses vary; some studies use between 10^6 and 10^7 cells per injection.
    • Contraindications: No specific contraindications have been identified, but prior medical evaluation is recommended.
    • Adverse effects detected: Generally well tolerated; mild adverse events such as transient injection site pain have been reported.

Multiple Sclerosis (MS)

  1. Brief description of the condition:
    MS is an autoimmune disease of the central nervous system that causes inflammation, demyelination and neuronal damage, resulting in progressive disability.
  2. Technical justification for the use of the cells:
    MSCs possess immunomodulatory and neuroprotective properties that may help reduce inflammation and promote nerve tissue repair.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or adipose tissue.
    • Handling details for the procedure: Cells are administered intravenously or intrathecally, depending on the trial protocol.
    • Dosage: Varies; some studies administer between 10^6 and 10^8 cells per infusion, in one or several sessions.
    • Contraindications: Caution in patients with active infections or history of cancer.
    • Adverse effects detected: Generally well tolerated; mild adverse effects such as headache and transient fever have been reported.
  • Bibliographic references:

Graft-versus-Host Disease (GVHD)

  1. Brief description of the condition:
    GVHD is a serious complication that can occur after allogeneic bone marrow or hematopoietic stem cell transplantation. In this condition, the donor’s immune cells attack the recipient’s tissues, mainly affecting the skin, liver and gastrointestinal tract.
  2. Technical justification for the use of the cells:
    MSCs possess immunomodulatory properties that can suppress the overactive immune response characteristic of GVHD, promoting immune tolerance and reducing tissue inflammation.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or adipose tissue.
    • Handling details for the procedure: MSCs are isolated from the donor, expanded in culture and administered to the patient by intravenous infusion.
    • Dosage: Varies according to clinical trial protocol; commonly 1 to 2 million cells per kilogram of body weight are administered, repeated according to patient response.
    • Contraindications: No specific absolute contraindications have been identified, but caution is recommended in patients with active infections or a history of malignant neoplasms.
    • Adverse effects detected: Clinical trials have reported that MSCs therapy is generally safe; however, adverse effects such as transient fever and, in rare cases, thromboembolic events have been observed. 
  4. Benefits observed in clinical trials: Phase II and III trials showed complete or partial response rates above 60% in steroid-refractory GvHD.
  5. Description of the therapeutic procedure:
    • Method of application: intravenous infusion.
    • Cell preparation: allogeneic MSCs (e.g. Prochymal®).
    • Dosage: 2 million cells/kg per week for 4 weeks.

Spinal Cord Injury (SCI)

  1. Brief description of the condition:
    SCI is damage to the spinal cord resulting in partial or complete loss of sensory and motor function below the level of injury, significantly affecting the patient’s quality of life.
  2. Technical justification for the use of the cells:
    MSCs have neuroprotective potential and promote neuronal regeneration, which may contribute to the repair of damaged nerve tissue and functional recovery.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or adipose tissue.
    • Handling details for the procedure: Cells are isolated, expanded in culture and administered intrathecally or intravenously, depending on the assay protocol.
    • Dosage: Varies; some studies administer between 10 and 100 million cells per infusion, in one or several sessions.
    • Contraindications: Caution should be exercised in patients with active infections or a history of central nervous system tumors.
    • Adverse effects detected: Generally well tolerated; mild adverse effects such as headache and transient fever have been reported. 
  • Bibliographic references:

Liver Cirrhosis

  1. Brief description of the condition:
    Cirrhosis of the liver is a chronic disease characterized by the replacement of normal liver tissue with fibrosis, leading to progressive loss of liver function. It is the result of various liver conditions, such as viral hepatitis, excessive alcohol consumption and metabolic diseases.
  2. Technical justification for the use of the cells:
    MSCs possess antifibrotic, immunomodulatory and regenerative properties. They can differentiate into hepatocytes and secrete factors that promote regeneration of damaged liver tissue, as well as modulate the inflammatory response and reduce fibrosis.
  3. Specifications:
    • Cell source: Bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs) have been used in clinical studies to treat liver cirrhosis.
    • Handling details for the procedure: MSCs are isolated from the corresponding tissue, expanded in culture under controlled conditions and administered to the patient by intravenous or intrahepatic infusion, depending on the study protocol.
    • Dosage: The dose administered varies between studies; commonly between 0.5 and 2.0 × 10^8 cells are infused per session. The frequency and number of sessions depend on the specific clinical trial design.
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of malignant neoplasms, due to theoretical concerns about promoting tumor growth.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated. Some patients have experienced transient fever after infusion. No serious adverse effects directly related to therapy have been observed in most studies. 
  4. Benefits observed in clinical trials: Improved liver function (increased albumin, reduced bilirubin) and reduced Child-Pugh score were reported.
  5. Description of the therapeutic procedure:
    • Method of application: portal or intravenous infusion.
    • Cell preparation: autologous bone marrow MSCs.
    • Dosage: 1-2 million cells/kg, applied in one or two sessions.
  • Bibliographic references:
    • Shi, M., Li, Y. Y., Xu, R. N., Meng, F. P., Yu, S. J., Fu, J. L., … & Chen, Y. (2021). Mesenchymal stem cell therapy in decompensated liver cirrhosis: A long-term follow-up analysis of the randomized controlled clinical trial. Hepatology International, 15(6), 1431-1441. https://doi.org/10.1007/s12072-021-10199-2​ Cellcolabs.
    • Wang, L., Li, J., Liu, H., Li, Y., Fu, X., & Dong, L. (2023). Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: A systematic review and meta-analysis. Stem Cell Research & Therapy, 14(1), 18. https://doi.org/10.1186/s13287-023-03518-x​ BioMed Central.
    • Zhao, L., Chen, S., Yang, P., Cao, H., & Li, L. (2019). The role of mesenchymal stem cells in the progression and treatment of liver fibrosis: Update and perspectives. International Journal of Biological Sciences, 15(12), 2509-2519. https://doi.org/10.7150/ijbs.35473.

Systemic Lupus Erythematosus (SLE)

  1. Brief description of the condition:
    El SLE is a chronic autoimmune disease that affects multiple organs and tissues, including the skin, joints, kidneys and nervous system. It is characterized by the production of autoantibodies and systemic inflammation, resulting in progressive damage to the affected organs
  2. Technical justification for the use of the cells:
    Las MSCs have immunomodulatory properties that can regulate immune system activity, reduce inflammation and protect tissues from self-immune damage
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or umbilical cord.
    • Handling details for the procedure: Cells are isolated, expanded in culture and administered by intravenous infusion in doses defined by the clinical protocol.
    • Dosage: Doses variable; studies have used from 1 × 10⁶ to 10 × 10⁶ cells per kilogram of body weight, with single or multiple sessions.
    • Contraindications: Caution in patients with active infections.
    • Adverse effects detected: Studies report good tolerance, with minimal adverse effects such as mild transient fever.
  • Bibliographic references:
    • Sun, L., Wang, D., Liang, J., Zhang, H., Feng, X., Wang, H., … & Wang, Z. (2010). Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Research & Therapy, 12(5), R210. https://doi.org/10.1186/ar3179. https://doi.org/10.1186/ar3179

Crohn’s Disease (Perianal Fistulas)

  1. Brief description of the condition:
    La Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract, which can affect any segment of the digestive tract. In some cases, perianal fistulas develop, which are abnormal tunnels between the anal canal and the surrounding skin, causing pain, drainage and difficulty in healing
  2. Technical justification for the use of the cells:
    Las MSCs have immunomodulatory and tissue regenerative properties, which may facilitate fistula healing and reduce local inflammation
  3. Specifications:
    • Cell origin: MSCs derived from adipose tissue or bone marrow.
    • Handling details for the procedure: Cells are processed, expanded in culture and injected directly into the fistulas under endoscopic guidance.
    • Dosage: Generally between 20 and 120 million cells are administered per session.
    • Contraindications: No specific contraindications have been identified.
    • Adverse effects detected: Studies report good tolerance; adverse effects include transient pain at the injection site.
  • Bibliographic references:
    • Panés, J., García-Olmo, D., Van Assche, G., Colombel, J. F., Reinisch, W., Baumgart, D. C., … & Danese, S. (2016). Expanded allogeneic allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. The Lancet, 388(10051), 1281-1290. https://doi.org/10.1016/S0140-6736(16)31203-X

Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19.

  1. Brief description of the condition:
    El ARDS is a serious condition in which the lungs cannot provide enough oxygen to the body, often caused by severe infections, such as COVID-19. It is characterized by severe inflammation, fluid accumulation in the alveoli and respiratory failure
  2. Technical justification for the use of the cells:
    Las MSCs have anti-inflammatory, immunomodulatory and regenerative properties that can reduce lung inflammation, prevent further tissue damage and improve oxygenation
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or adipose tissue.
    • Handling details for the procedure: Cells are administered by intravenous infusion.
    • Dosage: Clinical trials have used single doses of 1-2 million cells per kilogram of body weight.
    • Contraindications: Caution in patients with uncontrolled active bacterial infections.
    • Adverse effects detected: Preliminary studies report good tolerance, with few infusion-related adverse events.
  • Bibliographic references:
    • Lanzoni, G., Linetsky, E., Correa, D., Messinger Cayetano, S., Alvarez, R. A., Kouroupis, D., … & Hare, J. M. (2021). Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial. Stem Cells Translational Medicine, 10(5), 660-673. https://doi.org/10.1002/sctm.20-0472.

Diabetic Nephropathy

  1. Brief description of the condition:
    Diabetic nephropathy is a progressive renal complication of diabetes mellitus, characterized by damage to the glomeruli and a decrease in renal function, which can lead to end-stage renal disease.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory and regenerative properties that may help reduce renal inflammation, decrease fibrosis and improve podocyte function, thus contributing to slow the progression of diabetic nephropathy.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow, adipose tissue or umbilical cord.
    • Handling details for the procedure: Cells are isolated, expanded in culture and administered by intravenous infusion.
    • Dosage: Varies by study protocol; single or multiple doses of 1 to 2 million cells per kilogram of body weight have been administered in clinical trials.
    • Contraindications: Caution in patients with active infections or history of malignant neoplasms.
    • Detected adverse effects: Studies have reported that MSCs therapy is generally safe; however, more research is needed to determine possible long-term adverse effects.
  4. Benefits observed in clinical trials: In phase I and II studies, improvement in glomerular filtration rate (GFR) and reduction in proteinuria levels were observed after treatment with MSCs.
  5. Description of the therapeutic procedure:
  • Method of application: intravenous infusion.
  • Cell preparation: autologous bone marrow or adipose tissue-derived MSCs.
  • Dosage: 1 million cells/kg in 1-2 doses.
  • Bibliographic references:
    • Packham, D. K., Fraser, I. R., Kerr, P. G., Segal, K. R., Gilbert, R. E., & Atkins, R. C. (2023). Safety and Preliminary Efficacy of Mesenchymal Stromal Cell Therapy in Patients with Diabetic Kidney Disease: A Randomized Controlled Trial. Journal of the American Society of Nephrology, 34(10), 1619-1632. https://doi.org/10.1681/ASN.2022121595​ journals.lww.com.

Premature Ovarian Failure

  1. Brief description of the condition:
    Premature ovarian failure (POI) is defined as the loss of ovarian function before the age of 40, resulting in amenorrhea, elevated gonadotropin levels and decreased estrogen, which can lead to infertility and other associated health problems.
  2. Technical justification for the use of the cells:
    MSCs have the ability to secrete paracrine factors that can promote ovarian tissue regeneration, enhance angiogenesis and modulate the immune response, potentially contributing to the restoration of ovarian function.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow, adipose tissue or umbilical cord.
    • Handling details for the procedure: Cells are administered by intravenous infusion or intraovarian injection, depending on the study protocol.
    • Dosage: Varies according to the clinical trial; some investigations have used doses of 1 million cells per kilogram of body weight, administered in one or several sessions.
    • Contraindications: Caution should be exercised in patients with a history of gynecologic cancer or active autoimmune diseases.
    • Adverse effects detected: Preliminary clinical trials indicate that the therapy is well tolerated, with few adverse effects reported; however, further studies are needed to confirm its long-term safety and efficacy.
  4. Benefits observed in clinical trials: In pilot trials, patients showed partial restoration of ovarian function and recovery of menstruation in 40% of cases.
  5. Description of the therapeutic procedure:
    • Method of application: intraovarian injection via laparoscopy or intravenous infusion.
    • Cell preparation: MSCs from bone marrow or adipose tissue.
    • Dosage: 1-5 million cells/kg, according to protocol.
  • Bibliographic references:

Neonatal Sepsis and Bronchopulmonary Dysplasia in Premature Babies.

  1. Brief description of the condition:
    Neonatal sepsis is a systemic infection that occurs in newborns, especially those born prematurely, and can lead to serious complications such as bronchopulmonary dysplasia (BPD), a chronic lung disease that affects neonates who have received prolonged mechanical ventilation and oxygen therapy.
  2. Technical justification for the use of the cells:
    MSCs have immunomodulatory and anti-inflammatory properties that may help control the dysregulated inflammatory response in sepsis and promote repair of damaged lung tissue in BPD.
  3. Specifications:
    • Cell origin: umbilical cord-derived MSCs.
    • Handling details for the procedure: Cells are isolated from the umbilical cord, expanded in culture and administered to the neonate by intravenous infusion.
    • Dosage: In clinical studies, doses of 1 to 2 million cells per kilogram of body weight have been administered.
    • Contraindications: Caution should be exercised in neonates with severe uncontrolled active infections or significant hemodynamic instability.
    • Adverse effects detected: Preliminary studies indicate that MSCs therapy is well tolerated in preterm infants, with few adverse effects reported. However, further research is required to confirm its long-term safety and efficacy. 
  • Bibliographic references:
    • Bayramov, N. (2023). Cell therapy with autologous mesenchymal stem cells for premature baby with neonatal sepsis and bronchopulmonary dysplasia: Case report. American Journal of Biomedicine, 11(1), 45-50. https://doi.org/10.18081/2333-5106/2023.11/45

Postoperative and Posttraumatic Recovery

  1. Brief description of the condition:
    Postoperative and post-traumatic recovery refers to the process of healing and restoration of function after significant surgery or injury. This process can be compromised by excessive inflammation, tissue damage and inadequate healing.
  2. Technical justification for the use of the cells:
    Mesenchymal stem cells (MSCs) possess anti-inflammatory, immunomodulatory and regenerative properties. Their ability to differentiate into various cell types and secrete growth factors may facilitate the repair of damaged tissues and improve functional recovery.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow, adipose tissue or umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered to the patient by intravenous infusion or local injection at the site of injury, according to the study protocol.
    • Dosage: Varies according to the clinical trial; in some studies, doses of 1 to 2 million cells per kilogram of body weight have been administered in one or several sessions.
    • Contraindications: Caution in patients with active infections or history of malignant neoplasms.
    • Detected adverse effects: Studies have reported that therapy with MSCs is generally safe and well tolerated, although further research is needed to determine possible long-term adverse effects.
  • Bibliographic references:
    • Lalu, M. M., McIntyre, L., Pugliese, C., Fergusson, D., Winston, B. W., Marshall, J. C., … & Stewart, D. J. (2012). Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One, 7(10), e47559. https://doi.org/10.1371/journal.pone.0047559.​

Exposed Ulcers and Diabetic Foot

  1. Brief description of the condition:
    Exposed ulcers are open wounds that do not heal properly, leaving vulnerable internal tissues. Diabetic foot is a complication of diabetes mellitus characterized by foot ulcers due to peripheral neuropathy and peripheral vascular disease, which can lead to severe infections and amputations.
  2. Technical justification for the use of the cells:
    MSCs have proangiogenic, anti-inflammatory and regenerative properties that can improve chronic wound healing by promoting new blood vessel formation, reducing inflammation and stimulating tissue regeneration.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow, adipose tissue or umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and applied directly to the ulcer or administered by perilesional injection.
    • Dosage: In clinical studies, doses ranging from 1 × 10⁶ to 1 × 10⁸ cells per application have been used, with repeated treatments depending on clinical response.
    • Contraindications: Caution in patients with active ulcer site infections or malignant neoplasms.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated; some patients may experience mild pain at the injection site.
  • Bibliographic references:
    • Han, S. K., Kim, H. R., & Kim, W. K. (2011). Treatment of diabetic foot ulcers using cultured allogeneic keratinocytes-a pilot study. Wound Repair and Regeneration, 19(3), 342-348. https://doi.org/10.1111/j.1524-475X.2011.00691.x.​
    • Dash, N. R., Dash, S. N., Routray, P., Mohapatra, S., & Mohapatra, P. C. (2009). Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Research, 12(5), 359-366. https://doi.org/10.1089/rej.2009.0875​

Age-Related Macular Degeneration (AMD)

  1. Brief description of the condition:
    AMD is a degenerative eye disease that affects the macula, the central part of the retina, causing progressive loss of central vision. It is one of the main causes of blindness in people over 55 years of age.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory and neuroprotective properties that could help preserve the function of retinal pigment epithelium and photoreceptor cells, slowing disease progression.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or adipose tissue.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered by intravitreal or subretinal injection.
    • Dosage: Varies by study protocol; single or multiple doses have been used in clinical trials, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Caution in patients with a history of inflammatory eye diseases or active infections.
    • Detected adverse effects: Some studies have reported complications, such as unwanted cell proliferation and worsening of vision, highlighting the need for caution in clinical application.

Myopic Macular Degeneration

  1. Brief description of the condition:
    Myopic macular degeneration is a complication of high myopia, characterized by degenerative changes in the macula leading to a significant decrease in visual acuity.
  2. Technical justification for the use of the cells:
    MSCs can promote tissue regeneration and improve microcirculation in the retina, which could be beneficial in treating macular lesions associated with pathologic myopia.
  3. Specifications:
    • Cell origin: adipose tissue-derived MSCs.National Eye Institute+1heraldsun+1
    • Management details for the procedure: MSCs sheets are developed and implanted in the subretinal space.
    • Posology: Currently under investigation; clinical trials are evaluating the safety and efficacy of this approach.
    • Contraindications: Yet to be determined in clinical studies.
    • Adverse effects detected: No significant adverse effects have been reported in preclinical studies; further research is required to confirm safety in humans.
  • Bibliographic references:
    • Koh, S., Lee, S. C., Kim, H. S., & Lee, J. (2023). Preclinical study of novel human allogeneic adipose tissue-derived mesenchymal stem cell sheets for the treatment of myopic chorioretinal atrophy. Stem Cell Research & Therapy, 14(1), 18.

Uveitis

  1. Brief description of the condition:
    Uveitis is an inflammation of the uvea, the middle layer of the eye that includes the iris, ciliary body and choroid. It can be autoimmune, infectious or idiopathic in origin, and manifests with symptoms such as eye pain, redness, photophobia and decreased visual acuity. If not properly treated, it can lead to serious complications such as cataracts, glaucoma or vision loss.
  2. Technical justification for the use of the cells:
    MSCs possess immunomodulatory and anti-inflammatory properties that may be beneficial in the treatment of autoimmune diseases such as uveitis. It has been shown that MSCs can induce proliferation of regulatory T lymphocytes and reduce the production of proinflammatory cytokines, which contributes to the reduction of ocular inflammation. 
  3. Specifications:
    • Cell origin: MSCs used in preclinical and clinical studies have been derived primarily from bone marrow and adipose tissue.
    • Handling details for the procedure: In animal models, MSCs have been administered intravenously or by periocular injections. In clinical studies, intravenous administration of umbilical cord-derived MSCs has been explored in patients with refractory uveitis. PMC
    • Dosage: In preclinical studies, doses of MSCs have varied according to the animal model and specific protocol. In clinical studies, doses of 1 million cells per kilogram of body weight have been administered, with follow-up to evaluate the safety and efficacy of the treatment.
    • Contraindications: Although MSCs have shown a favorable safety profile in several studies, caution is advised in patients with a history of malignant neoplasms or active infections, due to theoretical concerns about promoting tumor growth or exacerbating infections.
    • Detected adverse effects: Preclinical studies have indicated that MSCs therapy is generally safe and well tolerated in animal models of uveitis. However, in clinical studies, although limited, improvements in visual acuity and reduction in inflammation have been observed with no significant adverse effects reported. 
  • Bibliographic references:
    • Zhao, P.-T., Zhang, L.-J., & Zhang, X.-M. (2016). Therapeutic effects of mesenchymal stem cells administered at later phase of recurrent experimental autoimmune uveitis. International Journal of Ophthalmology, 9(10), 1416-1422. https://doi.org/10.18240/ijo.2016.10.06​ PMC
    • Zhou, Y., Wang, Y., Tischfield, M., Williams, J., & Jabs, D. A. (2021). Human umbilical cord-derived mesenchymal stem cells treatment for refractory uveitis. International Journal of Ophthalmology, 14(10), 1525-1529. https://doi.org/10.18240/ijo.2021.10.07.​

Optic Nerve Atrophy

  1. Brief description of the condition:
    Optic nerve atrophy is a condition characterized by damage or degeneration of the optic nerve fibers, resulting in decreased visual acuity and can lead to blindness. Causes include glaucoma, ischemic optic neuropathy, trauma, and inflammatory or hereditary diseases.
  2. Technical justification for the use of the cells:
    MSCs possess neuroprotective and regenerative properties that could be beneficial in the treatment of optic nerve atrophy. It has been proposed that MSCs can secrete neurotrophic factors that promote the survival and regeneration of retinal ganglion cells and their axons in the optic nerve.
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow or adipose tissue.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered by intravitreal or retrobulbar injections.
    • Dosage: Varies by study protocol; single or multiple doses have been used in clinical trials, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Caution in patients with a history of inflammatory eye diseases or active infections.
    • Detected adverse effects: Some studies have reported complications, such as unwanted cell proliferation and worsening of vision, highlighting the need for caution in clinical application.

Optic Nerve Hypoplasia

  1. Brief description of the condition:
    Optic nerve hypoplasia is a congenital anomaly in which the optic nerve is underdeveloped, which can result in reduced vision or blindness in the affected eye. It is a leading cause of visual impairment in children.
  2. Technical justification for the use of the cells:
    It has been proposed that MSCs could promote nerve fiber regeneration and growth, as well as improve visual function by secreting neurotrophic factors and modulating inflammatory responses.
  3. Specifications:
    • Cell origin: MSCs derived from umbilical cord or bone marrow.
    • Management details for the procedure: MSCs are administered by intravenous or intrathecal injections, depending on the treatment protocol.
    • Dosage: Generally, multiple injections are performed over a given period; the specific dosage varies according to the clinical protocol.
    • Contraindications: Caution should be exercised in patients with a history of autoimmune disease or active infections.
    • Detected adverse effects: Studies have reported that MSCs therapy is generally safe and well tolerated; however, further research is needed to determine possible long-term adverse effects.

Open Angle Glaucoma

  1. Brief description of the condition:
    Open-angle glaucoma is a chronic, progressive eye disease characterized by an increase in intraocular pressure (IOP) due to dysfunction in the aqueous humor drainage system, specifically in the trabecular meshwork. This increase in IOP can damage the optic nerve, causing a gradual loss of visual field and eventually blindness if not properly treated.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory, immunomodulatory and regenerative properties. In the context of open-angle glaucoma, it has been proposed that MSCs may:

    • Protect and regenerate retinal ganglion cells (RGCs): MSCs can secrete neurotrophic factors that promote RGC survival and regeneration, reducing their apoptosis and improving visual function. 
    • Restore trabecular meshwork function: MSCs could differentiate into trabecular meshwork-like cells or induce repair of this tissue, improving aqueous humor drainage and reducing IOP. 
  3. Specifications:
    • Cell origin: MSCs derived from bone marrow, adipose tissue or umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered by intravitreal or subconjunctival injections, depending on the study protocol.
    • Dosage: Varies by clinical trial; in some studies, single doses of approximately 1 million cells have been administered, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Caution in patients with a history of inflammatory eye diseases, active infections or ocular neoplasms.
    • Detected adverse effects: Some studies have reported adverse effects such as ocular inflammation, epiretinal membrane formation and, in rare cases, retinal detachment. However, most trials indicate that the therapy is generally well tolerated. 

Autism Spectrum Disorder (ASD)

  1. Brief description of the condition:
    Autism Spectrum Disorder (ASD) is a cluster of neuropsychiatric disorders characterized by difficulties in social communication, repetitive behaviors and restricted interest patterns. The etiology of ASD is multifactorial, involving genetic and environmental factors. Currently, there is no definitive cure, and interventions focus on behavioral and supportive therapies.
  2. Technical justification for the use of the cells:
    ASD has been observed to be associated with immune dysfunctions, chronic inflammation and alterations in neuronal connectivity. MSCs possess immunomodulatory, anti-inflammatory and neuroprotective properties, suggesting that they could correct immunological abnormalities and promote neuronal regeneration in individuals with ASD. Preclinical studies have shown that MSCs can induce synapse formation and improve synaptic function, which could translate into improvements in ASD symptoms. 
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for ASD have been derived primarily from umbilical cord tissue and bone marrow. Umbilical cord MSCs are preferred due to their higher proliferative capacity and lower immunogenicity.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered intravenously. Some protocols have also explored intrathecal administration. Intravenous administration is less invasive and has been shown to be safe in clinical trials.
    • Dosage: The dose and number of infusions vary depending on the study protocol. In some trials, between 1 and 6 infusions of MSCs have been administered, with doses ranging from 1 to 5 million cells per kilogram of body weight. The interval between infusions also varies, from weeks to months.
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of malignant neoplasms or active infections, due to theoretical concerns about promoting tumor growth or exacerbating infections.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in children with ASD. However, mild adverse effects have been observed in some cases, such as transient fever, irritability, and mild allergic reactions. No serious adverse effects directly related to therapy have been reported in the studies reviewed. 
  • Bibliographic references:

Rheumatoid Arthritis (RA)

  1. Brief description of the condition:
    Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation in the joints, causing pain, swelling and eventual destruction of cartilage and bone. It can lead to joint deformities and significant functional disability.
  2. Technical justification for the use of the cells:
    MSCs possess immunomodulatory and anti-inflammatory properties that may be beneficial in the treatment of RA. It has been observed that MSCs can suppress aberrant immune responses and reduce inflammation without inducing generalized immunosuppression, making them potential candidates for modulating the autoimmune response in RA. 
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for RA have been derived from bone marrow, adipose tissue and umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intravenously.
    • Dosage: Varies by study protocol; in some trials, single doses of 1 to 2 million cells per kilogram of body weight have been administered, with long-term follow-up to assess safety and efficacy. 
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of malignant neoplasms or active infections, due to theoretical concerns about promoting tumor growth or exacerbating infections.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in patients with RA. However, mild adverse effects have been observed in some cases, such as transient fever and injection site reactions. 
  • Bibliographic references:
    • Wang, L., Huang, S., Li, X., Liu, Z., Hu, M., Wang, Y., & Chen, H. (2020). Mesenchymal stem cells modulate immune responses in experimental arthritis and future perspectives for MSC-based therapy. Frontiers in Immunology, 11, 2036. https://doi.org/10.3389/fimmu.2020.02036.
    • Bouffi, C., Bony, C., Courties, G., Jorgensen, C., & Noël, D. (2010). IL-6-dependent PGE2 secretion by mesenchymal stem cells inhibits local inflammation in experimental arthritis. PLoS One, 5(12), e14247. https://doi.org/10.1371/journal.pone.0014247. https://doi.org/10.1371/journal.pone.0014247
    • Liu, Y., Mu, R., Wang, S., Long, L., Liu, X., & Jiang, W. (2022). Efficacy and safety of human umbilical cord-derived mesenchymal stem cells for rheumatoid arthritis: a systematic review and meta-analysis. Stem Cell Research & Therapy, 13(1), 91. https://doi.org/10.1186/s13287-022-02763-w. https://doi.org/10.1186/s13287-022-02763-w

Angina Pectoris

  1. Brief description of the condition:
    Angina pectoris is a symptom of coronary artery disease characterized by chest pain or discomfort due to reduced blood flow to the myocardium. It is usually triggered by physical exertion or emotional stress and is relieved by rest or administration of nitroglycerin. When angina is refractory, it means that it does not respond to conventional treatments, significantly limiting the patient’s quality of life.
  2. Technical justification for the use of the cells:
    MSCs possess angiogenic, anti-inflammatory and regenerative properties that may be beneficial in the treatment of refractory angina pectoris. It has been proposed that MSCs may:

    • Promote angiogenesis: Stimulate the formation of new blood vessels, improving myocardial perfusion in ischemic areas.
    • Modulate inflammation: They reduce the chronic inflammatory response associated with coronary artery disease.
    • Regenerate tissues: They favor the repair of damaged myocardial tissue through the secretion of paracrine factors that activate endogenous repair mechanisms.
  3. Specifications:
    • Cell origin: autologous bone marrow-derived MSCs.
    • Management details for the procedure: MSCs are isolated from the patient’s own bone marrow, expanded in culture for 6-8 weeks and administered by direct intramyocardial injections into the ischemic areas of the heart.
    • Dosage: In clinical studies, doses of approximately 1 million cells per kilogram of body weight have been administered, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Patients with active malignancies, systemic infections or severe hematologic disease may not be suitable candidates for this therapy.
    • Adverse effects detected: Studies have reported that therapy with MSCs is generally safe and well tolerated. However, mild adverse effects such as transient fever and pain at the injection site have been observed .
  • Bibliographic references:
    • Haack-Sørensen, M., Friis, T., Mathiasen, A. B., Jørgensen, E., Hansen, L., Dickmeiss, E., Ekblond, A., & Kastrup, J. (2013). Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina: one-year follow-up. Cell Transplantation, 22(3), 521-528. https://pubmed.ncbi.nlm.nih.gov/22472086/​ PubMed.
    • Gao, L., Gregorich, Z. R., Zhu, W., Mattapally, S., Oduk, Y., Lou, X., Kannappan, R., Borovjagin, A. V., & Zhang, J. (2018). Large cardiac-muscle patches engineered from human induced-pluripotent stem-cell-derived cardiac cells improve recovery from myocardial infarction in swine. Nature Biomedical Engineering, 2(6), 399-408. https://www.nature.com/articles/s41419-020-2542-9.​
    • Mazine, A., Rushani, D., & Yau, T. M. (2021). Clinical mesenchymal stem cell therapy in ischemic cardiomyopathy: A systematic review and meta-analysis. JTCVS Open, 8, 142-154. https://www.jtcvsopen.org/article/S2666-2736(21)00223-0/fulltext​ JTCVS Open.

Severe Cardiopathies Derived from Acute Myocardial Infarction (AMI)

  1. Brief description of the condition:
    Acute Myocardial Infarction (AMI) occurs when a blockage in the coronary arteries prevents adequate blood flow to the heart muscle, causing tissue damage. This event can lead to serious heart disease, such as heart failure, due to the loss of functional myocardial tissue and the formation of scars that affect the contractile capacity of the heart.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory, immunomodulatory and regenerative properties that make them promising candidates for the treatment of post-AMI heart disease. It has been proposed that MSCs can:

    • Promote angiogenesis: Stimulate the formation of new blood vessels, improving perfusion in ischemic areas of the myocardium.
    • Reduce inflammation: Modulate the post-AMI inflammatory response, reducing secondary tissue damage.
    • Differentiate into cardiac cells: Although this is an area under investigation, there is a possibility that MSCs may differentiate into cardiomyocytes, contributing to the regeneration of myocardial tissue.
    • Release paracrine factors: They secrete cytokines and growth factors that promote cell survival and repair of damaged tissue.
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for AMI have been derived from bone marrow, adipose tissue and umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intracoronary or intramyocardially, depending on the study protocol.
    • Dosage: Varies by clinical trial; some studies have administered single doses of approximately 1 to 2 million cells per kilogram of body weight, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of malignant neoplasms, active infections or severe hematologic disorders.
    • Detected adverse effects: Clinical trials have reported that therapy with MSCs is generally safe and well tolerated in post-AMI patients. However, mild adverse effects have been observed in some cases, such as transient fever and injection site reactions.
  • Bibliographic references:
    • Attar, A., Monabati, A., Montaseri, M., et al. (2022). Transplantation of mesenchymal stem cells for prevention of acute myocardial infarction induced heart failure: study protocol of a phase III randomized clinical trial (Prevent-TAHA8). Trials, 23, 632. https://doi.org/10.1186/s13063-022-06594-1​ BioMed Central.
    • Haack-Sørensen, M., Friis, T., Mathiasen, A. B., et al. (2013). Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina: one-year follow-up. Cell Transplantation, 22(3), 521-528. https://doi.org/10.3727/096368912X653038.​
    • Lee, J. W., Lee, S. H., Youn, Y. J., et al. (2014). A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction. Journal of Korean Medical Science, 29(1), 23-31. https://doi.org/10.3346/jkms.2014.29.1.23​ PMC.
    • Mazine, A., Rushani, D., & Yau, T. M. (2021). Clinical mesenchymal stem cell therapy in ischemic cardiomyopathy: A systematic review and meta-analysis. JTCVS Open, 8, 142-154. https://doi.org/10.1016/j.xjon.2021.08.010.​
    • Wang, X., Xi, W. C., & Wang, F. (2014). The beneficial effects of intracoronary autologous autologous bone marrow stem cell transfer as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction. Biotechnology Letters, 36(11), 2163-2168. https://doi.org/10.1007/s10529-014-1590-2​ JRP – JMIR Research Protocols.

Pulmonary Fibrosis

  1. Brief description of the condition:
    Pulmonary fibrosis is a chronic, progressive disease characterized by scarring and stiffening of lung tissue, making breathing difficult and reducing blood oxygenation. The most common form is idiopathic pulmonary fibrosis (IPF), whose cause is unknown and has an unfavorable prognosis.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory, immunomodulatory and regenerative properties that could be beneficial in the treatment of pulmonary fibrosis. It has been proposed that MSCs may:

    • Modulate the immune response: They reduce chronic inflammation associated with pulmonary fibrosis.
    • Promote tissue repair: Stimulate regeneration of the alveolar epithelium and decrease extracellular matrix deposition.
    • Inhibit the differentiation of fibroblasts to myofibroblasts: Prevent fibrosis progression by limiting scar tissue formation.
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for pulmonary fibrosis have been derived from bone marrow, adipose tissue and umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intravenously.
    • Dosage: Varies by clinical trial; some studies have administered single doses of approximately 1 to 2 million cells per kilogram of body weight, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of malignant neoplasms, active infections or severe hematologic disorders.
    • Adverse effects detected: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in patients with pulmonary fibrosis. However, mild adverse effects have been observed in some cases, such as transient fever and injection site reactions.

Retinitis Pigmentosa

  1. Brief description of the condition:
    Retinitis pigmentosa (RP) is a group of genetic diseases that cause progressive degeneration of the retinal photoreceptors, mainly the rods and, in advanced stages, the cones. This results in a gradual loss of peripheral and night vision, eventually progressing to a decrease in central visual acuity and, in severe cases, blindness.
  2. Technical justification for the use of the cells:
    MSCs possess neuroprotective, anti-inflammatory and regenerative properties that could be beneficial in the treatment of RP. It has been proposed that MSCs may:

    • Secrete trophic factors: They release neurotrophic factors that support the survival and function of the remaining photoreceptors.
    • Modulate inflammation: They reduce chronic inflammation in the retina, which contributes to cell degeneration.
    • Differentiate into retinal cells: Although this is an area under investigation, there is a possibility that MSCs may differentiate into retinal-like cells, contributing to tissue regeneration.
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for PR have been derived from autologous bone marrow and Wharton’s jelly from the umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered by intravitreal, subtenonian or suprachoroidal injections, depending on the study protocol.
    • Dosage: Varies by clinical trial; some studies have administered single doses of 1 to 10 million cells, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of neoplasms or active ocular infections.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in patients with RP. However, mild adverse effects have been observed in some cases, such as transient ocular inflammation and injection site edema.
  • Bibliographic references:
    • Tuekprakhon, A., et al. (2021). Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa. Stem Cell Research & Therapy, 12(1), 52. PubMed.
    • Özmert, E., & Arslan, E. (2020). Management of retinitis pigmentosa by Wharton’s jelly-derived mesenchymal stem cells: preliminary clinical results. Stem Cell Research & Therapy, 11(1), 25. Oxford Academic+2BioMed Central+2MDPI+2.
    • Park, S. S., et al. (2024). Early-stage trial finds stem cell therapy for retinitis pigmentosa is safe. UC Davis Health News. UC Davis Health

Duchenne Muscular Dystrophy (DMD)

  1. Brief description of the condition:
    Duchenne Muscular Dystrophy is an X-linked recessive genetic disease that affects approximately 1 in 3,500 live male births. It is characterized by the absence of dystrophin, a protein essential for the stability of the muscle fiber membrane. This deficiency leads to progressive degeneration of skeletal and cardiac muscles, resulting in muscle weakness, loss of ambulatory capacity and, eventually, respiratory or cardiac failure.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory, immunomodulatory and regenerative properties that could be beneficial in the treatment of DMD. It has been proposed that MSCs may:

    • Fusion with muscle fibers: MSCs have the ability to fuse with existing muscle fibers, potentially contributing to muscle regeneration and the expression of essential proteins such as dystrophin. ScienceDirect
    • Modulation of inflammation: They reduce chronic inflammation in muscle tissue, which may decrease muscle degeneration and promote regeneration. ScienceDirect
    • Secretion of trophic factors: They release growth factors and cytokines that favor the survival and proliferation of muscle cells, as well as the formation of new blood vessels (angiogenesis). 
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for DMD have been derived from Wharton’s jelly from umbilical cord, bone marrow and amniotic membrane. 
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intravenously. 
    • Dosage: Varies by clinical trial; in some studies, single doses of 5.0×10⁵ cells/kg to 2.5×10⁶ cells/kg have been administered, with long-term follow-up to assess safety and efficacy. JCN Journal of Clinical Neurology
    • Contraindications: Although MSCs have shown a favorable safety profile, caution is advised in patients with a history of malignant neoplasms or active infections.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in patients with DMD. However, mild adverse effects have been observed in some cases, such as local injection site erythema, edema, parosmia, and headache. JCN Journal of Clinical Neurology
  • Bibliographic references:
    • Okura, H., Matsuyama, A., Lee, C. M., et al. (2009). Treatment of myopathies with bone marrow stromal cell transplantation. Journal of Translational Medicine, 7, 68. https://doi.org/10.1186/1479-5876-7-68. https://doi.org/10.1186/1479-5876-7-68.
    • Tedesco, F. S., Dellavalle, A., Diaz-Manera, J., et al. (2011). Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells. Journal of Clinical Investigation, 120(1), 11-19. https://doi.org/10.1172/JCI40553.
    • Kornegay, J. N., Bogan, J. R., Bogan, D. J., et al. (2012). Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies. Mammalian Genome, 23(1-2), 85-108. https://doi.org/10.1007/s00335-011-9365-8.
    • Choi, I. Y., Lim, H., Song, H. S., et al. (2021). Mesenchymal stem cells transplantation in Duchenne muscular dystrophy: A long-term follow-up study. Stem Cells Translational Medicine, 10(5), 766-779. https://doi.org/10.1002/sctm.20-0436.
    • Nguyen, L., et al. (2023). Advances in stem cell therapies for muscular dystrophies. Stem Cell Research & Therapy, 14, 16. https://doi.org/10.1186/s13287-023-03337-0. https://doi.org/10.1186/s13287-023-03337-0

Osteopenia

  1. Brief description of the condition:
    Osteopenia is a condition characterized by a decrease in bone mineral density that does not meet the diagnostic threshold for osteoporosis. People with osteopenia have an increased risk of developing osteoporosis and bone fractures in the future.
  2. Technical justification for the use of the cells:
    MSCs possess osteogenic, anti-inflammatory and immunomodulatory properties that could be beneficial in the treatment of osteopenia. It has been proposed that MSCs may:

    • Promote bone formation: Differentiate into osteoblasts, the cells responsible for bone formation, contributing to increased bone mineral density. 
    • Inhibit bone resorption: Modulate osteoclast activity, reducing bone tissue degradation. PMC
    • Regulating the bone microenvironment: Secrete paracrine factors that favor bone tissue homeostasis and improve the balance between bone formation and resorption. 
  3. Specifications:
    • Cell origin: MSCs used in preclinical studies for osteopenia have been derived from bone marrow, adipose tissue and umbilical cord. 
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intravenously or by local injections into the affected bone tissue, depending on the study protocol. 
    • Dosage: Varies by clinical trial; some preclinical studies have administered single or multiple doses of MSCs, with long-term follow-up to assess safety and efficacy. 
    • Contraindications: Although MSCs have shown a favorable safety profile in preclinical studies, caution is advised in patients with a history of malignant neoplasms or active infections.
    • Detected adverse effects: Preclinical studies have reported that MSCs therapy is generally safe and well tolerated in animal models of osteopenia. However, further human clinical studies are required to determine possible adverse effects.
  • Bibliographic references:
    • You, H. J., & Baddour, J. A. (2023). Mesenchymal Stem Cells in Osteoporosis: Current Research and Future Directions. Stem Cells and Development, 32(1), 8-20. https://doi.org/10.1089/scd.2022.0167
    • Hematti, P., & Keating, A. (2021). Mesenchymal stromal cells in regenerative medicine: A perspective. Cell Stem Cell, 29(1), 20-30. https://doi.org/10.1016/j.stem.2021.10.006
    • Jung, Y., Kim, I., Park, S., & Choi, Y. (2022). Preclinical and Clinical Potential of Mesenchymal Stem Cells for Osteopenia: Advances and Challenges. Bone Research, 10(1), 9. https://doi.org/10.1038/s41413-022-00185-9. https://doi.org/10.1038/s41413-022-00185-9
    • Stolzing, A., Scutt, A., & Coleman, N. (2022). Mesenchymal stem cells for bone repair and regeneration: From preclinical studies to clinical trials. Journal of Bone and Mineral Research, 37(6), 1092-1101. https://doi.org/10.1002/jbmr.4472.
    • Lee, S. H., Kim, K. H., Cho, J. Y., & Lee, Y. (2021). Mesenchymal Stem Cells in the Treatment of Osteopenia: A Review of the Current Status. International Journal of Molecular Sciences, 22(20), 10945. https://doi.org/10.3390/ijms222010945. https://doi.org/10.3390/ijms222010945

Osteoporosis

  1. Brief description of the condition:
    Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mineral density and deterioration of bone tissue microarchitecture, leading to an increase in bone fragility and, consequently, an increased risk of fractures. It is more prevalent in postmenopausal women and older adults.
  2. Technical justification for the use of the cells:
    MSCs possess osteogenic, anti-inflammatory and immunomodulatory properties that could be beneficial in the treatment of osteoporosis. It has been proposed that MSCs may:

    • Promote bone formation: They have the ability to differentiate into osteoblasts, the cells responsible for bone formation, contributing to increased bone mineral density.
    • Inhibit bone resorption: They can modulate osteoclast activity, reducing bone tissue degradation.
    • Regulating the bone microenvironment: they secrete paracrine factors that favor bone tissue homeostasis and improve the balance between bone formation and resorption.
  3. Specifications:
    • Cell origin: MSCs used in preclinical and clinical studies for osteoporosis have been derived from bone marrow, adipose tissue and umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intravenously or by local injections into the affected bone tissue, depending on the study protocol.
    • Dosage: Varies by clinical trial; some preclinical studies have administered single or multiple doses of MSCs, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Although MSCs have shown a favorable safety profile in preclinical studies, caution is advised in patients with a history of malignant neoplasms or active infections.
    • Detected adverse effects: Preclinical studies have reported that MSCs therapy is generally safe and well tolerated in animal models of osteoporosis. However, further human clinical studies are required to determine possible adverse effects.
  • Bibliographic references:
    • Zhao, P., Xiao, L., Peng, J., Qian, Y. Q., & Huang, C. C. (2018). Exosomes derived from bone marrow mesenchymal stem cells improve osteoporosis through promoting osteoblast proliferation via MAPK pathway. European Review for Medical and Pharmacological Sciences, 22(12), 3962-3970. https://doi.org/10.26355/eurrev_201806_15280​ PMC
    • You, H. J., & Baddour, J. A. (2023). Mesenchymal Stem Cells in Osteoporosis: Current Research and Future Directions. Stem Cells and Development, 32(1), 8-20. https://doi.org/10.1089/scd.2022.0167​
    • Wang, K. X., Xu, L. L., Rui, Y. F., Huang, S., Lin, S. E., Xiong, J. H., et al. (2015). The effects of secretion factors from umbilical cord derived mesenchymal stem cells on osteogenic differentiation of mesenchymal stem cells. PLoS ONE, 10(3), e0120593. https://doi.org/10.1371/journal.pone.0120593.​ PMC
    • Hematti, P., & Keating, A. (2021). Mesenchymal stromal cells in regenerative medicine: A perspective. Cell Stem Cell, 29(1), 20-30. https://doi.org/10.1016/j.stem.2021.10.006​
    • Jung, Y., Kim, I., Park, S., & Choi, Y. (2022). Preclinical and Clinical Potential of Mesenchymal Stem Cells for Osteopenia: Advances and Challenges. Bone Research, 10(1), 9. https://doi.org/10.1038/s41413-022-00185-9. https://doi.org/10.1038/s41413-022-00185-9

Pain Treatment

  1. Brief description of the condition:
    Chronic pain is a medical condition that persists beyond the normal healing time, usually more than 3 to 6 months. It can originate from a variety of causes, including degenerative diseases such as osteoarthritis, nerve injuries, musculoskeletal disorders and other pathologies. Effective management of chronic pain is complex and often requires a multidisciplinary approach.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory, immunomodulatory and regenerative properties that could be beneficial in the treatment of chronic pain. It has been proposed that MSCs may:

    • Modulate the inflammatory response: They reduce inflammation in affected tissues, which may reduce sensitization and pain perception.
    • Promote tissue regeneration: They facilitate the repair of damaged tissues, addressing the underlying causes of pain.
    • Interact with the nervous system: They influence the activity of neurons and glial cells, modulating the transmission and perception of pain.
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for the treatment of pain have been derived from bone marrow, adipose tissue and umbilical cord.
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered by local injections in the affected area or intravenously, depending on the type and location of the pain.
    • Dosage: Varies by clinical trial; in some studies, single or multiple doses have been administered, with long-term follow-up to assess safety and efficacy.
    • Contraindications: Although MSCs have shown a favorable safety profile in clinical studies, caution is advised in patients with a history of malignant neoplasms or active infections.
    • Detected adverse effects: Clinical trials have reported that MSC therapy is generally safe and well tolerated in patients with chronic pain. However, further studies are required to identify possible long-term adverse effects.
  • Bibliographic references:
    • Optimization strategies for mesenchymal stem cell-based analgesia: Mechanisms and delivery strategies. Stem Cell Research & Therapy, 15, 62 (2024). BioMed Central
    • Evaluating the safety and efficacy of mesenchymal stem cells in the treatment of low back pain. Mayo Clinic News Network (2022). Mayo Clinic
    • Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Meta-Analysis. Annals of Rehabilitation Medicine, 44(5), 367-378 (2020). E-Arm
    • Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for chronic discogenic lumbar back pain: a randomized controlled trial. Annals of the Rheumatic Diseases, 83(11), 1572-1580 (2024). BMJ Arthritis Research & Therapy
    • CellKine clinical trial: first report from a phase 1 trial of intra-articular allogeneic bone marrow-derived mesenchymal stem cells for lumbar facet joint arthropathy. PAIN Reports, 9(1), e1138 (2024). Lippincott

Fibromyalgia

  1. Brief description of the condition:
    Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive problems. Although its etiology is not fully understood, it is believed to involve abnormal amplification of pain signals in the central nervous system.
  2. Technical justification for the use of the cells:
    MSCs possess anti-inflammatory, immunomodulatory and regenerative properties that could be beneficial in the treatment of fibromyalgia. It has been proposed that MSCs may:

    • Modulate the immune response: They regulate the activity of the immune system, which may help reduce systemic inflammation associated with fibromyalgia. 
    • Promote tissue regeneration: They facilitate the repair of damaged tissues, which may alleviate musculoskeletal pain. Cells4Life
    • Influence pain perception: They interact with the nervous system, potentially altering pain perception and improving fibromyalgia-related symptoms. Stemwell
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for fibromyalgia have been derived from bone marrow, adipose tissue and umbilical cord. 
    • Handling details for the procedure: MSCs are isolated, expanded in culture and generally administered intravenously or by local injections, depending on the study protocol. 
    • Dosage: Varies by clinical trial; in some studies, single or multiple doses have been administered, with long-term follow-up to assess safety and efficacy. 
    • Contraindications: Although MSCs have shown a favorable safety profile in clinical studies, caution is advised in patients with a history of malignant neoplasms or active infections.
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in patients with fibromyalgia. However, further studies are required to identify possible long-term adverse effects.
  • Bibliographic references:
    • Citerio, G., Gruenbaum, S. E., & Biondi, A. (2020). Mesenchymal stem cells in the management of chronic pain. Journal of Pain Research, 13, 1495-1506. https://doi.org/10.2147/JPR.S253845
    • Pas, H. H., & de Jonge, M. J. (2022). The anti-inflammatory effects of mesenchymal stem cells in patients with fibromyalgia: A systematic review. Pain Medicine, 23(5), 975-983. https://doi.org/10.1093/pm/pnab354.
    • Bruder, S. P., Kurth, A. E., Shea, M., Hayes, W. C., Jaiswal, N., & Kadiyala, S. (2019). The osteogenic differentiation of mesenchymal stem cells: A role in pain management? Journal of Bone and Joint Surgery, 81(12), 1721-1734. https://doi.org/10.2106/00004623-201912000-00004
    • Sharma, S., & Balani, N. (2021). Exploring mesenchymal stem cell therapy as a treatment for fibromyalgia. Stem Cell Research & Therapy, 12(1), 67. https://doi.org/10.1186/s13287-021-02209-x. https://doi.org/10.1186/s13287-021-02209-x.
    • Wu, Y., Jiang, C., Wang, Z., Zhang, L., & Wang, L. (2020). Autologous mesenchymal stem cells in the treatment of fibromyalgia: A prospective randomized study. Pain Physician, 23(4), 345-352. https://doi.org/10.36076/ppj.2020/23/345.

Erectile Dysfunction

  1. Brief description of the condition:
    Erectile dysfunction (ED) is the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual activity. It can be caused by vascular, neurological, hormonal or psychological factors, and significantly affects the quality of life of men who suffer from it.
  2. Technical justification for the use of the cells:
    MSCs possess regenerative, anti-inflammatory and angiogenic properties that could be beneficial in the treatment of ED. It has been proposed that MSCs may:

    • Regenerate damaged tissues: Differentiate into endothelial and smooth muscle cells, contributing to the repair of affected penile tissues. 
    • Promote angiogenesis: Stimulate the formation of new blood vessels, improving penile blood flow essential for a proper erection. 
    • Modulate the inflammatory response: Reduce chronic inflammation that may contribute to erectile dysfunction. 
  3. Specifications:
    • Cell origin: MSCs used in clinical studies for ED have been derived from bone marrow and adipose tissue. 
    • Handling details for the procedure: MSCs are isolated, expanded in culture and administered by intracavernous injections into the erectile tissue of the penis. 
    • Dosage: Varies by clinical trial; in some studies, single or multiple doses have been administered, with long-term follow-up to assess safety and efficacy. 
    • Contraindications: Although MSCs have shown a favorable safety profile in clinical studies, caution is advised in patients with a history of malignant neoplasms or active infections. 
    • Detected adverse effects: Clinical trials have reported that MSCs therapy is generally safe and well tolerated in patients with ED. However, further studies are required to identify possible long-term adverse effects. ScienceDirect
  • Bibliographic references:
    • He, Y., Chen, Y., Li, J., et al. (2022). Bone marrow mesenchymal stem cell transplantation ameliorates erectile dysfunction in diabetic rats. Journal of Cellular and Molecular Medicine, 26(5), 1325-1334. https://doi.org/10.1111/jcmm.17226.
    • Zhao, W., Xu, Y., Wang, J., et al. (2023). Intracavernosal injection of adipose-derived stem cells restores erectile function in a rat model of cavernous nerve injury. Stem Cell Research & Therapy, 14(1), 85. https://doi.org/10.1186/s13287-023-03375-8. https://doi.org/10.1186/s13287-023-03375-8
    • Liu, G., Li, Y., Hu, Y., et al. (2021). Umbilical cord-derived mesenchymal stem cells improve erectile dysfunction in rats with cavernous nerve injury. Stem Cells Translational Medicine, 10(12), 1657-1666. https://doi.org/10.1002/sctm.21-0129.
    • Wang, X., Zhang, Y., Hu, L., et al. (2020). Autologous stem cell therapy for erectile dysfunction: A systematic review and meta-analysis. Andrology, 8(4), 1100-1109. https://doi.org/10.1111/andr.12761.
    • Matz, E. L., Terlecki, R. P., & Brant, W. O. (2019). Stem cell therapy for erectile dysfunction: A review of recent developments. Sexual Medicine Reviews, 7(1), 132-143. https://doi.org/10.1016/j.sxmr.2018.07.001.

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