皮肤干细胞毛囊再生研究

发布时间：2018-03-28 12:32

本文选题：表皮干细胞　切入点：真皮干细胞　出处：《清华大学》2016年博士论文

【摘要】：干细胞是人体各种组织细胞的最初来源,具有自我复制和分化能力,是生物及医学领域关注的焦点。干细胞可以用于组织器官的修复,为治疗许多重大疾病提供了新的思路和方法。皮肤是一个很好的用来研究器官再生的生物学和再生医学的模型。而毛囊作为一个微小器官,存在多种干细胞并受复杂信号通路调控。实现干细胞毛囊再生,不仅有助于研发功能更加完善的新一代组织工程皮肤,还能为干细胞器官再生提供理论依据。本论文研究中,我首先建立了表皮干细胞和真皮干细胞的分离和培养体系,并将两种扩增培养的皮肤干细胞移植到裸鼠的皮肤伤口中,实现了用扩增培养的皮肤干细胞再生毛囊。结果显示,表皮干细胞生成了新生皮肤的表皮和毛囊主体结构,而真皮干细胞形成了毛囊中的毛乳头以及真皮中的许多细胞。更进一步,我利用扩增培养的人源的两种皮肤干细胞,实现了完整毛囊的再生。这为临床运用皮肤干细胞进行皮肤再生奠定了基础。同时,我还针对真皮干细胞体外扩增稳定性的影响因素进行了研究,发现BMP4显著促进真皮干细胞毛囊诱导能力的维持。论文研究还显示,当两种皮肤干细胞在进行毛囊再生的时候,会伴随有皮脂腺的再生。在此基础上,我针对皮脂腺形成过程中的基因调控,找出了有效促进干细胞皮脂腺再生的分子组合。进一步研究显示,再生的皮脂腺与正常皮肤皮脂腺分泌的脂质成分相似,并有效保护皮肤减少皮肤水分的丢失。另外,论文还对支持干细胞毛囊再生的支架材料功能化自组装多肽水凝胶进行了研究,结果显示,RADA-PRG,一种含有RGD序列的混合多肽,在体外培养中可以有效地促进真皮干细胞的存活、增殖以及维持毛囊诱导能力相关基因的表达,并且在体内有效地支持皮肤干细胞再生毛囊,提示该材料具有较理想的组织工程支架材料的性能。
[Abstract]:Stem cells are the original source of various tissues and cells of the human body and have the ability to replicate and differentiate themselves. Stem cells are the focus of attention in biological and medical fields. Stem cells can be used for the repair of tissues and organs. It provides new ideas and methods for the treatment of many major diseases. Skin is a good model for studying biology and regenerative medicine of organ regeneration, and hair follicle is a small organ. There are a variety of stem cells regulated by complex signaling pathways. To achieve stem cell hair follicle regeneration is not only conducive to the development of a new generation of tissue engineering skin, but also provides a theoretical basis for stem cell organ regeneration. I first established a system of isolation and culture of epidermal stem cells and dermal stem cells, and transplanted two kinds of expanded and cultured skin stem cells into skin wounds of nude mice to regenerate hair follicles with expanded and cultured skin stem cells. Epidermal stem cells form the epidermis and hair follicle body structure of the newborn skin, and dermal stem cells form the dermal papilla in the hair follicle and many cells in the dermis. It lays the foundation for clinical application of skin stem cells for skin regeneration. At the same time, I also studied the factors that affect the stability of dermal stem cells expansion in vitro. It was found that BMP4 significantly promoted the ability of dermal stem cells to induce hair follicles. This study also showed that when two types of dermal stem cells regenerate hair follicles, they were accompanied by sebaceous gland regeneration. In view of the gene regulation of sebaceous gland formation, I have found a molecular combination that can effectively promote the regeneration of stem cell sebaceous glands. Further research shows that the regenerated sebaceous glands are similar to the lipid components secreted by normal skin sebaceous glands. In addition, the functional self-assembly polypeptide hydrogel of scaffold material supporting stem cell hair follicle regeneration was studied. The results showed that RADA-PRG, a mixed polypeptide containing RGD sequence, was used to prevent skin moisture loss. In vitro culture can effectively promote the survival and proliferation of dermal stem cells and maintain the expression of genes related to hair follicle induction ability, and effectively support the regeneration of dermal stem cells in vivo. It is suggested that the material has better properties of tissue engineering scaffold.
【学位授予单位】：清华大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q491.5

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