BONE MARROW STEM CELL BASED TISSUE MODULATING STRATEGY FOR WOUND HEALING

Abstract

THIS THESIS FIRST EXAMINES HOW MESENCHYMAL STEM CELLS (MSCS) INFLUENCE WOUND MICROENVIRONMENT THROUGH EXTRACELLULAR MATRIX (ECM) SECRETION. IT SHOWED THAT MSCS ARE STRONG SECRETORS OF ECM PROTEINS AND CAN MODULATE ITS ECM SECRETION IN RESPONSE TO WOUND HEALING RELATED CYTOKINE (TRANSFORMING GROWTH FACTOR-BETA1 AND TUMOR NECROSIS FACTOR-ALPHA) STIMULATION. MSC SECRETED MATRICES WERE ALSO STIMULATORY TO NORMAL HUMAN EPITHELIAL KERATINOCYTE (NHEKS) PROLIFERATION AND MOTILITY. WHEN CO-CULTURED IN CONTACT WITH NHEKS, MSCS WERE ABLE TO ENGAGE IN DERMAL-EPIDERMAL -LIKE INTERACTIONS TO DEPOSIT ECM PROTEINS OF THE DERMAL-EPIDERMAL JUNCTION. A TISSUE MODULATING SCAFFOLD THAT CONTAINS BIOACTIVE VITAMIN C, HYDROCORTISONE, INSULIN, TRIIODOTHYRONINE AND EPIDERMAL GROWTH FACTOR WAS THEN FABRICATED TO MODULATE WOUND HEALING AND IT SERVED AS A DELIVERY SYSTEM FOR MSCS. PILOT IN VIVO STUDIES WERE PERFORMED AND SHOWED THAT AS COMPARED TO SHAM WOUNDS, WOUND TREATED WITH THE TISSUE MODULATING SCAFFOLD-MS