An investigation of the use and delivery of mesenchymal stem cells and their secretome to treat skin wounds

Abstract

Skin damage can be caused by cuts, burns, abrasions and ulcers. Wound healing is a complex process involving coordination between multiple biological pathways and is classified into four stages: haemostasis, inflammation, proliferation, and tissue remodeling. Chronic wounds such as burn injuries and diabetic foot ulcer are under-appreciated injuries that are prevalent and life-threatening forms that contribute to mortality rates due to high rates of wound infections. Managing chronic wounds presents challenges and development of new therapeutics are required. Stem cells, specifically mesenchymal stem cells (MSCs), and their conditioned medium (CM) are known for their regenerative ability in skin wounds. However, there has been a need to search for an efficient delivery system for MSCs and its secretome for skin wounds. This thesis focused on using MySkinTM scaffolds as a delivery system for MSCs and MSC CM as these scaffolds were previously used in delivering keratinocytes for burn wounds. Initial experiments focused on an in vitro animal model using murine cells i.e., murine MSCs (ST2) and murine dermal fibroblasts (L929) where the results suggested that MSC CM helps accelerate dermal fibroblast adhesion/spreading, proliferation and migration. Furthermore, the animal model also suggested that it is possible to use culture MSCs on MySkinTM scaffolds and generate MSC CM on the scaffold. Additionally, the results also suggested that it is possible to deliver MSCs and MSC CM onto a wound site. The same set of experiments were conducted using human cells, i.e., human MSCs, dermal fibroblasts and endothelial cells. The results supported the findings from the animal model along with MSC CM supporting angiogenesis. Due to these results, the CM was analyzed for presence of growth factors, cytokines, chemokines, and extra cellular matrix (ECM) proteins which may have played a role in observing these results. The experiments suggest that it is possible to use and deliver MSCs and MSC CM using MySkinTM scaffolds and may help accelerate the wound healing process.