毛囊干细胞与组织工程研究进展

Research Progress of Hair Follicle Stem Cells and Tissue Engineering

毛囊干细胞研究取得突破性进展的标志是由孙同天、Lavker和Cotsarelis等提出了隆突激活假说,明确了其定位的部位,是少数几种成体干细胞首先被明确定位的干细胞之一,并逐步得到了验证。毛囊干细胞不仅可以分化为毛囊上皮细胞,而且可以分化为皮脂腺细胞、表皮角质形成细胞,其分化过程是干细胞分化为短暂倍增细胞,最后分化为终末分化细胞。近年来进一步证明了毛囊隆突部也是多种干细胞的居住地,包括黑素干细胞,和毛囊干细胞存在同步化激活的机制。Wnt/β-catenin是毛囊发育、再生循环的基本信号通路,使毛囊在再生过程出现着色一致的毛发。诱导和重建毛囊形成是组织工程皮肤最主要的目标之一,毛乳头细胞的凝集性生长特性是诱导毛囊形成的条件,因此,维持毛乳头细胞凝集性生长特性主要有细胞团块法、低黏附性培养板(或高分子材料膜)法、悬滴培养法和胶原凝胶成球法,以实现体外重建毛乳头的目的。毛囊组织工程在体外还不能真正诱导形成,现有的毛囊再生或新生的成功方法还是须移植到动物体内,才能形成完整毛囊并产生毛发。主要方法有移植小室法、混合游离细胞注射法和皮瓣法。诱导毛囊形成比较成功的细胞是啮齿类动物来源的胚胎或新生鼠毛囊细胞和人胚胎毛囊细胞,成年人头皮毛囊来源细胞目前仍未能诱导出毛囊新生或再生。

The milestone in research on stem cells of hair follicle is firstly to identify its location at the bulge of hair follicle called bulge activation hypothesis proposed by Sun TT,Lavker RM and Cotsarelis G. Follicular stem cell is one of few adult stem cells that have been clearly located. This hypothesis is gradually confirmed thereafter. The stem cells of hair follicle not only differentiate into epithelial cells of hair follicle,but also into sebaceous gland cells and epidermal keratinocytes. The process of their differentiation is from the stem cells to the transient amplifying cells and at end to the terminally differentiated cells. Recently,there has been demonstrated that other stem cells including melanocyte stem cells also located in the bulge. The hair follicle stem cells and melanocyte stem cells are co-ordinated activated. Wnt / β-catenin is the primary signal path of the development and regeneration of hair follicle,which synergisticly activate hair follicle stem cells and melanocyte stem cell for pigmented hair follicle regeneration. The main goal of tissue engineered skin grafts is to introduce and reconstruct the formation of hair follicle. The aggregative behavior of dermal papilla cells is an important condition for the introduction of hair follicle reformation. In order to maintain their aggregative character,there are some methods including cell clumps,low adhesion culture plate or high polymer material membrane,hanging drop and collagen gel sphere,which aim is to reform the dermal papillae in vitro. However,current tissue engineered skin cannot intrude hair follicle reformation in vitro. The regeneration and neogenesis of hair follicles now still needs to be transplanted into animal in vivo in order to reform integrity structure of hair follicle and to produce hair shaft. The main methods are the chamber assay,the patch assay that consists in injecting dissociated epidermal and dermal cells into adult mouse skin and the flap assay. Most of these experiments are successfully introduced hair follicle reformation using rodent cells,particularly from embryonic or newborn origin,and embryonic human cells,but no successful strategy to generate human hair follicles from adult cells has yet been reported.