Mesenchymal stem cell therapy for corneal diseases

ABSTRACT

Introduction: The transparency of human cornea is critical for normal vision. It is maintained by a small population of stem cells present in the corneal limbus. Corneal diseases are a major cause of global blindness, second only to cataract in overall importance. They are usually treated by medications and surgical modalities that sometimes include expensive and potentially toxic medications with long-term side effects, particularly to prevent rejection of the corneal allograft. Therefore, cell based therapies may provide a promising alternative to overcome these limitations for the treatment of corneal diseases.

Areas covered: This review article covers major sources, properties, and applications of mesenchymal stem cells in corneal reconstruction. This also includes a brief description of the structure, function, and immune privilege of the cornea; corneal stem cells, corneal diseases, available treatments, and potential of MSC-based cell therapy for corneal diseases.

Expert opinion: Technical advancements in corneal transplantation and development of explant culture techniques like cultivated limbal epithelial transplantation, cultivated oral mucosal epithelial transplantation, and simple limbal epithelial transplantation have resulted in improved outcomes for treating corneal diseases; however, the treatment for bilateral corneal diseases still remains elusive. The increased risk of allograft rejection and long term side-effects of immunosuppressive medications, calls for alternative cell based therapies. Mesenchymal stem cells, with their unique dual property of multipotency and immunomodulation, offer a promising approach towards treatment of bilateral corneal disorders. However, the parameters including mechanism of homing, transdifferentiation, immunomodulation, and the risk of rejection, the cell source and the number of cells, the time of injection, and the mode of delivery must be studied before translating the possible benefits of MSCs in corneal transplants to clinical practice.

KEYWORDS:

• Mesenchymal stem cells
• cornea
• limbal stem cell deficiency
• immunomodulation
• differentiation

Article highlights

• Corneal diseases affect not only the vision but also the quality of life.

• Limbal stem cells play a key role in maintenance of the corneal transparency and renewal of the corneal epithelium.

• The multipotent differentiation and immunomodulation properties of MSCs are the key for regeneration of injured limbal stem cells and for preventing corneal allograft rejection.

• MSCs are a promising tool for cell based therapies in severe bilateral corneal diseases (e.g. LSCD) where corneal transparency is compromised.

• Parameters like risk of rejection, cell source, number of cells to be injected, time of injection, and the mode of delivery must be studied before translating the possible benefits of MSCs to clinical practice.

• Further insights into the mechanism of MSC homing, transdifferentiation potential, and immunomodulation are required for successful clinical trials.

This box summarizes key points contained in the article.

Acknowledgements

Authors are highly thankful to Mr. S.B.N. Chary and Ms. Nazia for their help in providing photographs of the patients. We are also thankful to Ms. Rajashri Mokashi, Stemade Pvt. Ltd., Chennai, India, for providing the human dental pulp stem cells.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

S Shukla acknowledges funding and support from the INSPIRE Faculty grant [No. IFA14-LSBM-104], from the Department of Science and Technology, Govt. of India. V Singh acknowledges funding from grant [No. SB/YS/LS-263/2013], Department of Science and Technology (SERB), Govt. of India.