| Full-thickness skin defect wounds are one of the most common, complex, costly diseases. Wound healing is a normal process in response to soft tissue injury, which involves a highly organized cascade of events. If combine with infection or other diseases, even for the most superficial wounds, treatment is often difficult with poor healing responses and high rates of complications. Although several advanced technologies have been developed to improve the treatment of skin wounds, the infection of the wound or other diseases(diabetes et al.) may delayed the process of wound healing. This will not only bring pain to the patients, but also increase the consumption of medical resources. Wound healing includes many complex phases, and these phases include hemostasis, inflammation, proliferation, and remodeling. For a normal healing process, all of the above stages must function in a proper sequence and on specific times. Therefore, interference with any of the four stages during the wound healing can lead to impairment of the healing process. In most chronic wounds, the tissue regeneration is arrested in the inflammatory phase that leads to pathologic inflammation and failure of the endogenous repair response to progress to the advanced stages of wound healing. The continuous inflammatory phase leads to abnormal production of inflammatory cytokines. So novel methods of treating wound healing are especially important for clinical uses.In recent years, the bio-engineering technology has achieved great progress, bring lights to wound healing. Such as the adult stem cells, which has potential on helping human wound healing, by differentiating into multiple tissues cells or increasing wound epithelialization. Among these stem cells, the adipose-derived stem cells(ASCs), easily obtained, clinical safety, has more clinical value, compared with other tissue-derived stem cells. Adult stem cells on the other hand do not pose any ethical issues and are also available in abundant supply. To date, lot of researches have focused on bone marrow-derived stem cells(BMSCs). However, the procurement of these cells is a painful procedure and usually leads to low yield and may lead to donor site morbidity. On the other hand, stem cells derived from adipose tissue are easy to obtain and provide a much higher yield. When comparing these cells to BMSCs, they show similar morphology, differentiation potential, and cell surface markers. Transcriptomic and proteomics analysis also shows similar profile for ASCs and BMSCs. Due to their ease of collection and similar properties, ASCs are another attractive source and worthy of attention for clinical translation.ASCs as a kind of adult pluripotent stem cells, can also differentiate into various tissues cells, such as: epithelial cells, which can accelerate wound epithelialization, and promote wound healing; ASCs can also paracrine secretion of cytokines, stimulate tissue regeneration, such as: secretion of antigenic factors(vascular endothelial growth factor, VEGF) and other cytokines, controlled the development of inflammation, promote skin wound healing is ideal bioactive cells. SYNO1 is approved by the US Food and Drug Administration(FDA), which can promote wound healing, anti-infection by other means to accelerate wound healing, improve healing quality. These conclusions will further validates its function on wound healing, lay the foundation for clinical phase I applications.In the first part of this experiment, we aimed to use adipose-derived stem cells for in vitro treatment, to further clarify the characteristics of ASCs, including the extraction step from human and Yorkshire pig, identification methods, stem cell markers and tracers Method; in vivo experiments, we aim to use ASCs in Yorkshire pig dorsal skin wound model. The immunohistochemistry, PKH26 mark and other methods were used to evaluate the speed and quality of wound healing. The second part of our experiment is the treatment of SYNO1 on wound healing. In vitro experiments, we used SYNO1 on Resistant Staphylococcus aureus(MRSA) in a petri dish. In vivo experiments, we used SYNO1 in Yorkshire pig skin wound MRSA infection model for treatment.The results showed that Adipose-derived stem cells and SYNO1 can promote wound healing on Yorkshire pig back skin infection wound healing, control inflammation and infection, improve wound healing rate and quality. Although ASCs have shown to be effective in treatment of acute and chronic wounds in preclinical settings exact mechanism of their functions is still under investigation. It has been postulated that ASCs can initiate or enhance tissue regeneration by two different mechanisms, either by differentiating into skin cells or by secretion of paracrine factors, which can initiate the healing process via recruiting endogenous stem cells and ECs or down-regulating the inflammatory response. ASCs and their potential for wound healing treatment has been shown in several studies.The two novel treatments are promising on further clinical use. |
PDF Full Text Request