Wagner Wolfgang, Roderburg Christoph, Wein Frederik, Diehlmann Anke, Frankhauser Maria, Schubert Ralf, Eckstein Volker, Ho Anthony D
Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Stem Cells. 2007 Oct;25(10):2638-47. doi: 10.1634/stemcells.2007-0280. Epub 2007 Jul 5.
Mesenchymal stromal cells (MSC) provide a supportive cellular microenvironment and are able to maintain the self-renewal capacity of hematopoietic progenitor cells (HPC). Isolation procedures for MSC vary extensively, and this may influence their biologic properties. In this study, we have compared human MSC isolated from bone marrow (BM) using two culture conditions, from cord blood (CB), and from adipose tissue (AT). The ability to maintain long-term culture-initiating cell frequency and a primitive CD34(+)CD38(-) immunophenotype was significantly higher for MSC derived from BM and CB compared with those from AT. These results were in line with a significantly higher adhesion of HPC to MSC from BM and CB versus MSC from AT. We have compared the cytokine production of MSC by cytokine antibody arrays, enzyme-linked immunosorbent assay, and a cytometric bead array. There were reproducible differences in the chemokine secretion profiles of various MSC preparations, but there was no clear concordance with differences in their potential to maintain primitive function of HPC. Global gene expression profiles of MSC preparations were analyzed and showed that adhesion proteins including cadherin-11, N-cadherin, vascular cell adhesion molecule 1, neural cell adhesion molecule 1, and integrins were highly expressed in MSC preparations derived from BM and CB. Thus, MSC from BM and CB are superior to MSC from AT for maintenance of primitive HPC. The latter property is associated with specific molecular profiles indicating the significance of cell-cell junctions but not with secretory profiles. Disclosure of potential conflicts of interest is found at the end of this article.
间充质基质细胞（MSC）提供支持性细胞微环境，并能够维持造血祖细胞（HPC）的自我更新能力。MSC的分离程序差异很大，这可能会影响其生物学特性。在本研究中，我们比较了使用两种培养条件从骨髓（BM）、脐带血（CB）和脂肪组织（AT）中分离的人MSC。与来自AT的MSC相比，来自BM和CB的MSC维持长期培养起始细胞频率和原始CD34(+)CD38(-)免疫表型的能力显著更高。这些结果与HPC对来自BM和CB的MSC的粘附力明显高于对来自AT的MSC的粘附力一致。我们通过细胞因子抗体阵列、酶联免疫吸附测定和细胞计数珠阵列比较了MSC的细胞因子产生情况。各种MSC制剂的趋化因子分泌谱存在可重复的差异，但与它们维持HPC原始功能的潜力差异没有明显的一致性。对MSC制剂的整体基因表达谱进行了分析，结果显示，包括钙粘蛋白-11、N-钙粘蛋白、血管细胞粘附分子1、神经细胞粘附分子1和整合素在内的粘附蛋白在来自BM和CB的MSC制剂中高度表达。因此，对于维持原始HPC而言，来自BM和CB的MSC优于来自AT的MSC。后一种特性与表明细胞间连接重要性的特定分子谱相关，但与分泌谱无关。潜在利益冲突的披露见本文末尾。
