Daniel C P, Ponting I L, Dexter T M
Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
Haematol Blood Transfus. 1989;32:172-7. doi: 10.1007/978-3-642-74621-5_29.
The in vitro methods used to study haemopoiesis fall into two distinct categories. Short-term colony forming assays have identified a number of potent soluble factors capable of maintaining survival, proliferation and differentiation of haemopoietic cells but not their self-renewal. In contrast, in long-term bone marrow culture, extensive self-renewal occurs in the absence of exogenous factors and direct physical contact between haemopoietic cells and cells of the adherent stromal layer seems to be important. Obviously, LTBMC more closely resembles the situation in haemopoietic tissues but the potency of growth factors imply that they too play a role. Our data suggest that this may be at an earlier stage of haemopoietic development than previously appreciated. Primitive multipotent cells have the potential to respond to CSFs which were previously thought to stimulate only committed progenitor cells. This response is only seen, however, when the cells are exposed to a combination of factors which include either IL-1 or G-CSF. Thus, a combination of factors is able to recruit cells which are not already committed and determine the lineage along which they will differentiate. While it remains to be conclusively demonstrated that growth factors regulate normal "steady state" haemopoiesis in vivo it is clear that contact with stromal cells is important. The mechanisms by which the adherent layer influences haemopoietic development, however, are less obvious. We have shown that a component of stroma, heparan sulphate, is able to bind growth factors and present them to haemopoietic cells in a way that stimulates haemopoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)
用于研究造血作用的体外方法可分为两类。短期集落形成试验已鉴定出一些能维持造血细胞存活、增殖和分化但不能维持其自我更新的强效可溶性因子。相比之下，在长期骨髓培养中，在没有外源性因子的情况下会发生广泛的自我更新，造血细胞与贴壁基质层细胞之间的直接物理接触似乎很重要。显然，长期骨髓培养更类似于造血组织中的情况，但生长因子的效力表明它们也发挥作用。我们的数据表明，这可能发生在造血发育的比之前认为的更早阶段。原始多能细胞有潜力对集落刺激因子作出反应，而这些因子以前被认为只刺激定向祖细胞。然而，只有当细胞暴露于包括白细胞介素-1或粒细胞集落刺激因子在内的多种因子组合时，才会出现这种反应。因此，多种因子的组合能够募集尚未定向的细胞，并确定它们将分化的谱系。虽然仍有待确凿证明生长因子在体内调节正常的“稳态”造血作用，但与基质细胞的接触很重要这一点是明确的。然而，贴壁层影响造血发育的机制尚不明显。我们已经表明，基质的一种成分硫酸乙酰肝素能够结合生长因子，并以刺激造血的方式将它们呈递给造血细胞。（摘要截选至250词）
