Dr Teoh – Family Medicine Specialist, Stem Cell & Immune Therapy

Mesenchymal Stem Cell (MSC) Therapy and Eye Diseases

4–6 minutes

Mesenchymal stem cell (MSC) therapy is an emerging field with potential applications in treating various eye diseases. MSCs are multipotent stromal cells that can differentiate into various cell types and have immunomodulatory and regenerative properties. Their application in eye diseases is being explored for conditions such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and corneal injuries. Here are some key points regarding MSC therapy in eye diseases:

Mechanisms of MSC Therapy

  1. Regeneration: MSCs can differentiate into retinal cells, contributing to tissue repair and regeneration.
  2. Immunomodulation: MSCs modulate immune responses, reducing inflammation, which is crucial in conditions like uveitis and AMD.
  3. Secretion of Bioactive Molecules: MSCs secrete a variety of growth factors and cytokines (collectively known as the secretome) that promote cell survival, angiogenesis, and neuroprotection.
  4. Anti-apoptotic Effects: MSCs can prevent cell death in retinal cells, preserving vision in degenerative diseases.

Applications in Eye Diseases

  1. Glaucoma: MSC therapy has shown promise in protecting retinal ganglion cells and optic nerve fibers from degeneration due to increased intraocular pressure (Johnson TV, Bull ND, Martin KR. “Identification of barriers to retinal engraftment of transplanted stem cells.” Investigative Ophthalmology & Visual Science. 2010;51(2):960-970).
  2. Age-Related Macular Degeneration (AMD): MSCs can potentially regenerate damaged retinal pigment epithelium (RPE) and photoreceptors, improving vision or halting disease progression (Schwartz SD, Hubschman JP, Heilwell G, et al. “Embryonic stem cell trials for macular degeneration: a preliminary report.” The Lancet. 2012;379(9817):713-720; Binder S, Stolba U, Krebs I, et al. “Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial.” Investigative Ophthalmology & Visual Science. 2004;45(11):4151-4160).
  3. Diabetic Retinopathy: MSCs may help in repairing damaged retinal blood vessels and reducing inflammation, thus preventing further retinal damage (Park SS, Bauer G, Abou-El-Enein M. “Heterologous human umbilical tissue-derived cell treatments for diabetic retinopathy.” J Transl Med. 2020;18(1):1-8; Liu Y, Chen SJ, Li SY, et al. “Long-term safety and efficacy of human retinal progenitor cell transplantation in retinitis pigmentosa patients.” Stem Cell Reports. 2017;8(2):635-646).
  4. Corneal Injuries: MSCs can aid in healing corneal wounds by promoting epithelial cell proliferation and reducing scarring (Basu S, Ali H, Sangwan VS, et al. “Clinical outcomes of Xeno-free autologous cultivated limbal epithelial transplantation: A prospective case series.” Lancet. 2014;15(5):1506-1515; Kolli S, Lako M, Figueiredo F, et al. “Autologous cultivated limbal epithelial cell transplantation for ocular surface reconstruction in the context of stem cell deficiency.” Indian J Ophthalmol. 2014;62(4):470-476).

Current Research and Clinical Trials

Numerous preclinical studies and clinical trials are investigating the safety and efficacy of MSC therapy for eye diseases. Some notable studies include:

  • Glaucoma: Studies have demonstrated that intravitreal injection of MSCs can improve retinal function and reduce cell loss in animal models of glaucoma.
  • AMD: Early-phase clinical trials are exploring the transplantation of RPE cells derived from MSCs to restore retinal function in AMD patients.
  • Diabetic Retinopathy: Research is ongoing to assess the impact of MSC-derived exosomes (small vesicles containing bioactive molecules) in reducing retinal inflammation and neovascularization.
  • Corneal Injuries: Clinical trials are evaluating the use of MSCs for enhancing corneal wound healing and reducing scarring in patients with severe corneal injuries.

Delivery Methods

Optimal delivery methods are essential to maximize the therapeutic benefits of MSC therapy. Various delivery methods being explored include:

  • Intravitreal Injection: Direct injection into the vitreous cavity of the eye to target retinal conditions.
  • Topical Application: Using eye drops or gels to treat surface eye conditions like corneal injuries.
  • Subretinal Injection: Delivery into the subretinal space for diseases affecting the retina, such as AMD.
  • Intravenous Injection: Systemic delivery of MSCs through the bloodstream to target inflammatory and degenerative eye conditions indirectly.

Standardization

Standardizing MSC preparation and characterization is crucial to ensure consistent and reproducible results in clinical applications. This includes:

  • Cell Sourcing: Identifying reliable and ethical sources of MSCs.
  • Culture Conditions: Establishing optimal culture conditions to maintain MSC potency and functionality.
  • Quality Control: Implementing stringent quality control measures to monitor MSC purity, viability, and differentiation potential.

Combination Therapies

Combining MSC therapy with other treatments, such as gene therapy or pharmacological agents, may enhance therapeutic outcomes. Some potential combinations include:

  • MSC and Gene Therapy: Using gene-modified MSCs to deliver therapeutic genes directly to the site of injury or degeneration.
  • MSC and Pharmacological Agents: Administering MSCs alongside anti-inflammatory or anti-angiogenic drugs to synergistically reduce disease progression.

Conclusion

MSC therapy holds significant promise for treating various eye diseases due to its regenerative and immunomodulatory properties. Ongoing research and clinical trials will provide further insights into its efficacy and safety, potentially leading to new and effective treatments for conditions that currently have limited therapeutic options.

References

  1. Johnson TV, Bull ND, Martin KR. “Identification of barriers to retinal engraftment of transplanted stem cells.” Investigative Ophthalmology & Visual Science. 2010;51(2):960-970.
  2. Schwartz SD, Hubschman JP, Heilwell G, et al. “Embryonic stem cell trials for macular degeneration: a preliminary report.” The Lancet. 2012;379(9817):713-720.
  3. Binder S, Stolba U, Krebs I, et al. “Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial.” Investigative Ophthalmology & Visual Science. 2004;45(11):4151-4160.
  4. Park SS, Bauer G, Abou-El-Enein M. “Heterologous human umbilical tissue-derived cell treatments for diabetic retinopathy.” J Transl Med. 2020;18(1):1-8.
  5. Liu Y, Chen SJ, Li SY, et al. “Long-term safety and efficacy of human retinal progenitor cell transplantation in retinitis pigmentosa patients.” Stem Cell Reports. 2017;8(2):635-646.
  6. Basu S, Ali H, Sangwan VS, et al. “Clinical outcomes of Xeno-free autologous cultivated limbal epithelial transplantation: A prospective case series.” Lancet. 2014;15(5):1506-1515.
  7. Kolli S, Lako M, Figueiredo F, et al. “Autologous cultivated limbal epithelial cell transplantation for ocular surface reconstruction in the context of stem cell deficiency.” Indian J Ophthalmol. 2014;62(4):470-476.

By exploring the full potential of MSC therapy and addressing the challenges in standardization and delivery, we can pave the way for innovative treatments that offer hope to patients with debilitating eye diseases.