The Chinese University of Hong Kong (CUHK), Hong Kong
Abstract: Diabetic foot ulcers (DFUs) represent a major complication of diabetes, often leading to poor healing outcomes with conventional treatments. Mesenchymal stem cell (MSC) therapies have emerged as a promising alternative, given their potential to modulate various pathways involved in wound healing. While diverse MSC sources have been explored, consensus is lacking on optimal donor specifications. This study evaluates and compares the therapeutic potential of MSCs derived from perinatal tissues—human umbilical cord MSCs (hUCMSCs), human chorionic villi MSCs (hCVMSCs), and human decidua basalis MSCs (hDCMSCs)—in a diabetic wound healing model. In our study, keratinocyte proliferation, re-epithelialization, collagen deposition, and angiogenesis were assessed through immunofluorescence and histological analyses. Our research results demonstrated that MSCs from perinatal tissues, particularly hUCMSCs and hCVMSCs, significantly enhanced diabetic wound healing and promote keratinocyte proliferation and vascular regeneration in db/db mice, whereas hDCMSCs were less effective. Mass spectrometry revealed a conserved set of proteins involved in extracellular matrix (ECM) organization and wound healing, with the PI3K/AKT signaling pathway playing a central role in these processes. Additionally, The PEGDA/SA/Col-I hydrogel supported the viability and function of MSCs, offering a promising scaffold for the treatment of DFUs. In another rat model of wound healing, the combined therapy of local MSC-encapsulated hydrogels with systemic administration of stem cell secretome demonstrated a stronger repair function compared to local hydrogel-stem cell encapsulation treatment alone.". These findings highlight the potential of specific perinatal MSCs and optimized hydrogel formulations in advancing diabetic wound care, offering new strategies for clinical treatment of diabetic wound healing.
Funding Source: Hong Kong Innovation and Technology Commission (MHP/024/19 and ITS/448/18) National Key Research and Development Program of China (2019 YFE0198400)
