Stem cell bandages – an investigation into the therapeutic effect of adipose-derived mesenchymal stem cells in corneal wound healing

Abstract

Human corneal regenerative capacity is not enough to heal deep injuries that causes scars, such abrasions result in the formation of the irregular extracellular matrix that leads to scar and often results in corneal transparency and vision reduction. Because of the limited number of corneal donors for transplantation, there has been an increased interest in cell therapy. Adipose-derived stem cells (ASCs) showed a promising choice for they are environmentally responsive in wound repair. ASCs can secrete paracrine factors and extracellular molecules that have immunomodulatory, angiogenic, trophic, anti-fibrotic, and antimicrobial activity. This thesis explores the formation of bandages; such bandages are formed of sodium alginate. Alginates are present in nature and extracted from brown seaweed. Generally, this material is safe, cost-effective, and wildly used in biomedical applications due to its biocompatibility and ease of handling. Hypothermic temperatures are also explored in here for bandage storage. Hence, this project hypothesized the formation of hypothermically stored ASCs bandages and their beneficial effect on corneal injuries. ASCs bandages were found to improve in vitro corneal scratch wounds, while storage at 15°C presented a favorable condition to store the bandages to vastly enhance their therapeutic potential. This storage is suggested to be a hypoxia-induced environment that augments cells ability to produce paracrine factors. Thus, hypoxia-induced ASCs bandages showed a promising therapeutic ability in healing corneal injures. Gene assessment and protein array revealed the production of several paracrine factors including HGF, TSG-6, IL-8, MCP1, TSP-1 that aid in wound healing. In vivo, hypoxia-induced ASCs bandages were transferred to adult male mice corneas following a chemical burn, where reduction of immune cell infiltration was observed. Thus, supporting this thesis hypothesis.