Dexter T M, Heyworth C M, Spooncer E, Ponting I L
Cancer Research Campaign Laboratories, Paterson Institute for Cancer Research, Christie Hospital, Withington, Manchester, UK.
Philos Trans R Soc Lond B Biol Sci. 1990 Mar 12;327(1239):85-98. doi: 10.1098/rstb.1990.0045.
Haemopoietic stem cells in vivo proliferate and develop in association with stromal cells of the bone marrow. Proliferation and differentiation of haemopoietic stem cells also occurs in vitro, either in association with stromal cells or in response to soluble growth factors. Many of the growth factors that promote growth and development of haemopoietic cells in vitro have now been molecularly cloned and purified to homogeneity and various techniques have been described that allow enrichment (to near homogeneity) of multipotential stem cells. This in turn, has facilitated studies at the mechanistic level regarding the role of such growth factors in self-renewal and differentiation of stem cells and their relevance in stromal-cell mediated haemopoiesis. Our studies have shown that at least some multipotential cells express receptors for most, if not all, of the haemopoietic cell growth factors already characterized and that to elicit a response, several growth factors often need to be present at the same time. Furthermore, lineage development reflects the stimuli to which the cells are exposed, that is, some stimuli promote differentiation and development of multipotential cells into multiple cell lineages, whereas others promote development of multipotential cell into only one cell lineage. We suggest that, in the bone marrow environment, the stromal cells produce or sequester different types of growth factors, leading to the formation of microenvironments that direct cells along certain lineages. Furthermore, a model system has been used to show the possibility that the self-renewal probability of multipotential cells can also be modulated by the range and concentrations of growth factors present in the environment. This suggests that discrete microenvironments, preferentially promoting self-renewal rather than differentiation of multipotential cells, may also be provided by marrow stromal cells and sequestered growth factors.
体内造血干细胞与骨髓基质细胞共同增殖和发育。造血干细胞的增殖和分化也可在体外发生，可与基质细胞共同培养，也可对可溶性生长因子产生反应。目前，许多促进体外造血细胞生长和发育的生长因子已被分子克隆并纯化至同质，还描述了多种技术可用于富集（至接近同质）多能干细胞。这反过来又促进了在机制层面研究此类生长因子在干细胞自我更新和分化中的作用及其与基质细胞介导的造血作用的相关性。我们的研究表明，至少一些多能细胞表达了大多数（如果不是全部）已鉴定的造血细胞生长因子的受体，并且要引发反应，通常需要同时存在几种生长因子。此外，谱系发育反映了细胞所接触的刺激，也就是说，一些刺激促进多能细胞分化和发育为多个细胞谱系，而另一些刺激则促进多能细胞仅发育为一个细胞谱系。我们认为，在骨髓环境中，基质细胞产生或隔离不同类型的生长因子，导致形成指导细胞沿特定谱系发育的微环境。此外，已使用一个模型系统来证明环境中存在的生长因子的种类和浓度也可能调节多能细胞的自我更新概率。这表明骨髓基质细胞和隔离的生长因子也可能提供离散的微环境，优先促进多能细胞的自我更新而非分化。
