山羊毛囊干细胞构建毛囊化组织工程皮肤研究
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摘要
组织工程皮肤自发展20多年来取得了很大的进展,目前已有数种组织工程皮肤应用于临床,为大面积烧伤以及和各种原因引起的皮肤大面积溃烂患者带来了福音。但是,已有的组织工程皮肤只是在结构上具有了皮肤的屏障功能,而不能形成毛囊、汗腺和皮脂腺等皮肤附属器官。临床移植后发现,创面干燥、皴裂、缺乏韧性和弹性等,给患者造成一定的痛苦。因此,构建具有毛囊、汗腺等皮肤附属器官的组织工程皮肤是未来组织工程发展的方向。
     研究发现,皮肤中的干细胞主要位于毛囊外根鞘隆突部位,毛囊干细胞具有多能性,它们在相关信号的作用下,可向上迁移参与皮脂腺和表皮的形成,向下迁移参与毛囊的形成。因此,以毛囊干细胞为种子细胞构建具有毛囊的组织工程皮肤,是一个理想的方案。但是由于毛囊干细胞存在部位隐蔽,缺乏特异性表面标志,从而限制了毛囊干细胞的体外研究和应用。本研究从山羊毛囊干细胞分离、培养、生物学特性以及分化潜能等方面进行了研究,并以毛囊干细胞和毛囊真皮细胞为种子细胞构建组织工程皮肤。主要内容包括:
     1.山羊毛囊干细胞分离培养体系的建立
     2.山羊毛囊干细胞生物学特性研究
     3.组织工程皮肤构建、检测及移植
Tissue engineered skin has made a great progress in the last20years and some of them have been used in clinic, which have contributed greatly to the burned patient and skin ulcer patient.However, the tissue engineered skin have not the physiological function of normal skin because they are absent of skin appendiges, such as hair follicle, sweat gland and sebaceous gland.Therefor,when transplanted to the patient, the artificial skin without secretion and made the wound dried and chapped, so the patient would feel uncomfortable.Constructing a tissue engineered skin with appendages is the objective of tissue engineering skin.
     Some study showed that skin stem cells located in the hair follicle bulge and they were multipotent.The hair follicle stem cells can respond to morphogenetic signal to generate multiple hair follicle, sebaceous gland, and epidrmis. So hair follicle stem cells is the ideal seeded cells to construct a tissue engineered skin. Located secerated and without specific surface marker restricted the research and application of hair follicle stem cells in clinic. The present study reasearched the isolation, culture system and the biology of the hair follicle stem cells. We also constructed a tissue engineered skin with hair follicle stem cells and hair follicle dermal cells and then transplated to the goat modle. The details of the research include the following four points:
     1. Establishment of the optimal method for isolatin goat hair follicle stem cells and the culture system.
     2. Biology of goat hair follicle stem cells.
     4. Construction, assay and transplantation of tissue engineered skin
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