| Summary: | 碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 98 === Wound healing is a complex biological process regulated by a series of interaction of cells, cell signals, and intracellular matrix that helps maintain the skin integrity. Diabetes impairs multiple aspects of the wound healing response and the delayed wound healing resulting in prolonged hospitalization for diabetic patients. However, effective therapies for diabetic wound are still lacking. Several lines of evidences suggest that stem cells play an important role in wound healing. Various impaired wound-healing states might be due to a deficiency in the function of stem cells. The current work sought to determine whether epidermal stem cells (basal stem/progenitor cells or bulge stem cells) can accelerate wound healing in diabetic mice model. We initially demonstrate that, in the early stage of acute wound healing, some distal lining K10-positive cells co-expressed p63 and Keratin 14 suggesting de-differentiation may occur in the wound healing process. We also discovered there was an expansion of p63-positive stem/progenitor cells in the basal layer neighboring to the wounded site. To further determine whether epidermal stem cells involve in wound healing process, we used K5-CreER; Z/EG mice as a model which allow us to label either basal stem/progenitor cells or bulge stem cells with EGFP before creating full-thickness wound. Based on using this lineage-tracing technique, we found EGFP-positive cells were localized in suprabasal layer of healed wound. The results confirm the involvement of epidermal stem cells. Next, we tried to investigate whether transplantation of basal stem/progenitor cells and/or bulge stem cells would promote wound healing in nude mice. We found, in combination with dermal fibroblast, both types of stem cell transplantation can heal the wound efficiently. Noticeably, when transplantation of bulge stem cells together with dermal fibroblast to wound site of nude mice, we found new hairs were generated from healed wound. To achieve the aim of determining whether epidermal stem cells can accelerate diabetic wound healing. We characterized wound healing process in two different diabetic mice models including streptozotocin-induced diabetic (type I diabetic) mice, and db/db (type II diabetic) mice. Delay in healing process was seen in two models. Although disorganized distal lining K10-positive cells that co-expressed p63 and K14 can be identified, however, the number of p63-positive cells was relatively low and collagen synthesis was largely reduced comparing to normal wound healing. To examine whether transplantation of basal stem/progenitor cells and/or bulge stem cells would promote wound healing in db/db diabetic mice, we showed that transplantation of basal stem/progenitor cells could partially promote wound closure and restore collagen synthesis. Hopefully the current study would lead to improvement of treatment for non-healed wound in diabetic patients.
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