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

Ph. D. ThesisHuman 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

Tissue-Sparing Excision for Skin Lesions Located on the Lower Limb

Dermatology-oncolog

Hypothermically stored adipose-derived mesenchymal stromal cell alginate bandages facilitate use of paracrine molecules for corneal wound healing

Adipose-derived mesenchymal stromal cells (Ad-MSCs) may alleviate corneal injury through the secretion of therapeutic factors delivered at the injury site. We aimed to investigate the therapeutic factors secreted from hypothermically stored, alginate-encapsulated Ad-MSCs’ bandages in in vitro and in vivo corneal wounds. Ad-MSCs were encapsulated in 1.2% w/v alginate gels to form bandages and stored at 15 °C for 72 h before assessing cell viability and co-culture with corneal scratch wounds. Genes of interest, including HGF, TSG-6, and IGF were identified by qPCR and a human cytokine array kit used to profile the therapeutic factors secreted. In vivo, bandages were applied to adult male mice corneas following epithelial debridement. Bandages were shown to maintain Ad-MSCs viability during storage and able to indirectly improve corneal wound healing in vivo. Soluble protein concentration and paracrine factors such as TSG-6, HGF, IL-8, and MCP-1 release were greatest following hypothermic storage. In vivo, Ad-MSCs bandages-treated groups reduced immune cell infiltration when compared to untreated groups. In conclusion, bandages were shown to maintain Ad-MSCs ability to produce a cocktail of key therapeutic factors following storage and that these soluble factors can improve in vitro and in vivo corneal wound healing