Clonal Analysis of Hematopoiesis-Supporting Activity of Human Mesenchymal Stem Cells in Association With Jagged1 Expression and Osteogenic Potential
Clonal Analysis of Hematopoiesis-Supporting Activity of Human Mesenchymal Stem Cells in Association With Jagged1 Expression and Osteogenic Potential
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DOI：
10.3727/096368908787236611
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Iwata, Hiroo
中科院分区：
文献类型：
--
作者：
Fujita, Satoshi;Toguchida, Junya;Iwata, Hiroo
人骨髓间充质干细胞（hMSCs）是扩增造血干细胞（HSCs）的有前途的饲养细胞，但其潜力是异质的。我们在克隆水平上研究了hMSC的造血支持活性与成骨潜能和基因表达的关系。通过与人脐带血来源的CD 34（+）细胞共培养7天后CD 34（+）CD 38（-）细胞的扩增来评估稳定永生化克隆hMSC系的造血支持活性。16个克隆中有6个扩增了CD 34（+）CD 38细胞数>500倍。这些造血支持性克隆还显示出Notch配体Jagged 1的高基因表达，以及成骨诱导后存款钙的高潜力。因此，成骨hMSC克隆可以为HSC扩增提供适当的微环境，最终通过Notch途径将自我更新信号传递给HSC。然而，它们在成骨分化后失去了造血支持活性。造血支持克隆是潜在的有用的造血微环境的研究，并作为一个共培养系统的组成部分，用于扩大HSC，从异种病原体的污染自由。
Human mesenchymal stem cells (hMSCs) are promising feeder cells for expanding hematopoietic stem cells (HSCs), but their potential is heterogeneous. We examined the hematopoiesis-supporting activity of hMSC at the clonal level in relation to the osteogenic potential and gene expression. Hematopoiesis-supporting activities of stably immortalized clonal hMSC lines were evaluated by the expansion of CD34(+)CD38(-) cells after 7-day coculture with human cord blood-derived CD34(+) cells. Six of 16 clones expanded the numbers of CD34(+)CD38 cells >500-fold. These hematopoiesis-supportive clones also showed high gene expression of Jagged1, a Notch ligand, as well as high potential to deposit calcium after osteogenic induction. Thus, osteogenic hMSC clones may provide proper microenvironments for HSC expansion, ultimately conveying self-renewal signals to HSCs via the Notch pathway. However, they lost hematopoiesis-supporting activity after osteogenic differentiation. The hematopoiesis-supportive clones are potentially useful for hematopoietic microenvironment studies and as components of a coculture system for expansion of HSCs, free from contamination by xenogeneic pathogens.