Department of Tumorimmunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Stem Cells Dev. 2013 Apr 1;22(7):1086-96. doi: 10.1089/scd.2012.0384. Epub 2012 Dec 21.
Bone marrow (BM) stromal cells (MSCs), also known as mesenchymal stem cells, display a high degree of heterogeneity. To shed light on the causes of this heterogeneity, MSCs were collected from either human BM (n=5) or adipose tissue (AT) (n=5), and expanded using 2 different culture methods: one based on fetal calf serum, and one based on human platelet lysate. After initial expansion, MSCs were frozen, and the vials were transported to 3 different laboratories and grown for 1 passage using the same brand of culture plastic, medium, and supplements. Subsequently, the cells were harvested and assayed for their gene expression profile using the Affymetrix exon microarray platform. Based on gene expression profiles, the most discriminative feature was the anatomical harvesting site, followed by culture methodology. Remarkably, genes in the WNT pathway were expressed at higher levels in BM-derived MSCs than in AT-derived MSCs. Although differences were found between laboratories, cell culture location only slightly affects heterogeneity. Furthermore, individual donors contributed marginally to the observed differences in transcriptomes. Finally, BM-derived MSCs displayed the highest level of similarity, irrespective their culture conditions, when compared to AT-derived cells.
骨髓(BM)基质细胞(MSCs),也称为间充质干细胞,表现出高度的异质性。为了阐明这种异质性的原因,我们从人类 BM(n=5)或脂肪组织(AT)(n=5)中收集 MSC,并使用 2 种不同的培养方法进行扩增:一种基于胎牛血清,另一种基于人血小板裂解物。初始扩增后,MSC 被冷冻,并将小瓶运送到 3 个不同的实验室,使用相同品牌的培养塑料、培养基和补充剂进行 1 个传代培养。随后,使用 Affymetrix 外显子微阵列平台收集细胞并检测其基因表达谱。基于基因表达谱,最具鉴别特征的是解剖采集部位,其次是培养方法。值得注意的是,WNT 通路中的基因在 BM 来源的 MSC 中的表达水平高于 AT 来源的 MSC。尽管在实验室之间存在差异,但细胞培养位置仅对异质性产生轻微影响。此外,观察到的转录组差异主要由个体供体贡献。最后,与 AT 来源的细胞相比,BM 来源的 MSC 显示出最高的相似性,无论其培养条件如何。