Macrophage inflammatory protein 1 alpha, interleukin 3 and diffusible marrow stromal factors maintain human hematopoietic stem cells for at least eight weeks in vitro.
Macrophage inflammatory protein 1 alpha, interleukin 3 and diffusible marrow stromal factors maintain human hematopoietic stem cells for at least eight weeks in vitro.
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巨噬细胞炎症蛋白1α，白细胞介素3和可扩散的骨髓基质因子在体外至少维持人类造血干细胞至少八周。
DOI：
10.1084/jem.179.2.643
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发表时间：
1994-02-01
影响因子：
15.3
通讯作者：
Li, W N
中科院分区：
文献类型：
--
作者：
Verfaillie, C M;Catanzarro, P M;Li, W N
诱导人造血干细胞增殖的因素不明确。原始造血祖细胞可以在基质依赖性长期骨髓培养物（LTBMC）中维持和分化，最初由Dexter等人描述（Dexter，T. M.，L. H. Coutinho，E.斯普恩瑟角M.海沃思角P.丹尼尔，R. Schiro，J. Chang，and T. D.艾伦。1990.造血的分子控制）。然而，70-80%的原始祖细胞能够重新启动次级基质培养物（LTBMC起始细胞[IC]）在5周的时间内丢失。我们最近描述了一种新的“基质非接触”培养系统，其中造血祖细胞与基质层分离的0.4微米微孔滤膜。这种培养物中的原始祖细胞不仅可以分化成定向祖细胞，而且比“Dexter”培养物中的原始祖细胞更大程度地被维持。然而，在第5周时仍仅回收50%的最初接种的LTBMC-IC。由于原始祖细胞的维持可能不仅依赖于生长促进因子，还依赖于抑制分化和/或增殖的因子，因此我们评估了巨噬细胞炎性蛋白1 α（MIP-1 α）或“干细胞抑制剂”与生长诱导因子白细胞介素3（IL-3）组合对从基质非接触培养物中回收LTBMC-1C的作用。我们证明，添加MIP-1 α单独的基质非接触培养不改变LTBMC-IC的数量后8周，表明该因子可能不会直接抑制或刺激原始祖细胞的增殖。单独添加生长刺激细胞因子IL- 3导致培养8周后LTBMC-IC耗尽，这可能是其终末分化的结果。然而，当在补充有MIP-1 α和IL-3的基质非接触培养物中生长时，LTBMC-IC可以维持至少8周。这种效应依赖于可溶性（不明确的）基质因子，并且是由这些细胞因子与祖细胞群体或其后代而不是基质的直接相互作用引起的。
Factors that induce proliferation of the human hematopoietic stem cell are ill-defined. Primitive hematopoietic progenitors can be maintained and differentiate in stroma-dependent, long-term bone marrow cultures (LTBMC), originally described by Dexter et al. (Dexter, T. M., L. H. Coutinho, E. Spooncer, C. M. Heyworth, C. P. Daniel, R. Schiro, J. Chang, and T. D. Allen. 1990. Molecular Control of Haemopoiesis). However, 70-80% of primitive progenitors capable of reinitiating secondary stromal cultures (LTBMC-initiating cells [IC]) are lost over a period of 5 wk in such cultures. We have recently described a novel "stroma-noncontact" culture system, in which hematopoietic progenitors are separated from the stromal layer by a 0.4-micron microporous filter membrane. Primitive progenitors in such cultures can not only differentiate into committed progenitors, but are also maintained to a greater extent than in "Dexter" cultures. However, still only 50% of the originally seeded LTBMC-IC are recovered at week 5. Since maintenance of primitive progenitors may depend not only on growth- promoting factors but also on factors that inhibit differentiation and/or proliferation, we evaluated the effect of macrophage inflammatory protein 1 alpha (MIP-1 alpha) or "stem cell inhibitor" in combination with the growth-inducing factor interleukin 3 (IL-3) on the recovery of LTBMC-IC from stroma-noncontact cultures. We demonstrate that addition of MIP-1 alpha alone to stroma-noncontact cultures does not change the number of LTBMC-IC present after 8 wk, indicating that this factor may not directly inhibit or stimulate proliferation of primitive progenitors. Addition of the growth stimulatory cytokine, IL- 3, alone results in exhaustion of LTBMC-IC after 8 wk of culture, possibly as a result of their terminal differentiation. However, LTBMC- IC can be maintained for at least 8 wk when grown in stroma-noncontact cultures supplemented with both MIP-1 alpha plus IL-3. This effect depends on soluble (ill-defined) stromal factors, and results from a direct interaction of these cytokines with the progenitor population or its progeny, but not the stroma.