Importance of Parenchymal: Stromal Cell Ratio for the Ex Vivo Reconstitution of Human Hematopoiesis
Importance of Parenchymal: Stromal Cell Ratio for the Ex Vivo Reconstitution of Human Hematopoiesis
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实质的重要性：基质细胞比率对于人类造血的离体重建
DOI：
10.1002/stem.150305
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发表时间：
1997
期刊：
影响因子：
5.2
通讯作者：
B. Palsson
中科院分区：
文献类型：
--
作者：
M. Koller;I. Manchel;B. Palsson
组织工程的许多新进展依赖于由实质和间充质（基质）细胞群组成的原代组织的培养。由于基质调节实质功能，实质：基质细胞（P：S）比例可能会影响培养行为。为了研究实质-基质细胞相互作用，在人骨髓（BM）培养系统中系统性改变P：S比，测量成熟细胞、未成熟祖细胞（集落形成单位-粒细胞/巨噬细胞[CFU-GM]）和原始干细胞（长期培养起始细胞[LTC-IC]）的输出。当实质CD 34富集细胞在无基质的情况下生长时，细胞和CFU-GM产量随着接种密度的增加而线性增加，导致细胞和CFU-GM扩增比恒定。在辐照预成型基质（IPFS）上，培养物产量显著更高，对CD 34富集细胞接种密度的依赖性更低，导致在较低接种密度下的扩增率更高。支持CD 34富集细胞所需的IPFS细胞数量与CD 34富集细胞数量无关，表明IPFS不提供离散的小生境，而是通过可溶性信号起作用。使用来自IPFS的条件培养基（CM）的实验证实了可溶性信号的存在，但CM不能完全取代CD 34富集细胞与IPFS之间的直接接触。由于IPFS和基质在BM单核细胞（MNC）培养物中生长的已知差异，接下来使用MNC的CD 34富集和CD 34耗尽部分的混合物进行实验。当接种固定数量的CD 34 +lin−细胞时，培养物产量在未操作MNC样品的P：S比附近最佳，并随着CD 34 −细胞数量的增加或减少而下降。在接种固定总细胞数的培养物中，CFU-GM输出随着CD 34 +lin-细胞数的增加而增加，而LTC-IC输出达到平台期。这些数据表明，MNC间质中存在有限数量的LTC‐IC支持性小生境，而IPFS缺乏这些小生境，主要通过不太有效的可溶性机制发挥作用。这些研究强调了实质-基质细胞相互作用在组织功能离体重建中的重要性，并提供了对人BM培养系统中这些相互作用性质的深入了解。
Many new developments in tissue engineering rely on the culture of primary tissues which is composed of parenchymal and mesenchymal (stromal) cell populations. Because stroma regulates parenchymal function, the parenchymal:stromal cell (P:S) ratio will likely influence culture behavior. To investigate parenchymal‐stromal cell interactions, the P:S ratio was systematically varied in a human bone marrow (BM) culture system, measuring the output of mature cells, immature progenitors (colony forming units‐granulocyte/macrophage [CFU‐GM]), and primitive stem cells (long‐term culture‐initiating cells [LTC‐IC]). When parenchymal CD34‐enriched cells were grown without stroma, cell and CFU‐GM output increased linearly as inoculum density was increased, resulting in constant cell and CFU‐GM expansion ratios. On irradiated preformed stroma (IPFS), culture output was significantly higher and less dependent on CD34‐enriched cell inoculum density, resulting in greater expansion ratios at lower inoculum densities. The number of IPFS cells required to support CD34‐enriched cells was independent of the CD34‐enriched cell number, suggesting that IPFS did not provide discrete niches, but instead acted through soluble signals. Experiments using conditioned medium (CM) from IPFS confirmed the presence of soluble signals, but CM did not completely substitute for direct contact between CD34‐enriched cells and IPFS. Because of known differences between IPFS and stroma growing within BM mononuclear cell (MNC) cultures, experiments were next performed using mixtures of CD34‐enriched and CD34‐depleted fractions of MNC. When inoculated with a fixed CD34+lin− cell number, culture output was optimal near the P:S ratio of the unmanipulated MNC sample and declined as CD34− cell number was increased or decreased. In cultures inoculated with a fixed total cell number, CFU‐GM output increased as CD34+lin− cell number was increased, whereas LTC‐IC output reached a plateau. These data suggest that a limited number of LTC‐IC supportive niches were present in MNC stroma, whereas IPFS lacks these niches and acts predominantly through a less potent soluble mechanism. These studies underscore the importance of parenchymal‐stromal cell interactions in the ex vivo reconstitution of tissue function and offer insight into the nature of these interactions in the human BM culture system.
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与基质直接接触会抑制人类长期培养起始细胞的增殖。
影响因子：
11.4
作者：
Verfaillie,CM;Catanzaro,P
通讯作者：
Catanzaro,P
CD34细胞选择和灌注对外周血单核细胞离体扩增的影响。
影响因子：
20.3
作者：
Sandstrom,CE;Bender,JG;Papoutsakis,ET;Miller,WM
通讯作者：
Miller,WM
影响因子：
20.3
作者：
J. Cashman;A. Eaves;E. Raines;R. Ross;C. Eaves
通讯作者：
J. Cashman;A. Eaves;E. Raines;R. Ross;C. Eaves
血细胞细胞粘附分子。
影响因子：
2.6
作者：
Long,MW
通讯作者：
Long,MW
辅助细胞可降低人骨髓细胞扩增潜力的供体间差异，但可溶性生长因子不会降低这种差异。
DOI：
--
发表时间：
1996
期刊：
Experimental hematology.
影响因子：
--
作者：
Koller,MR;Manchel,I;Brott,DA;PalssonBo
通讯作者：
PalssonBo