School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
The University of Hong Kong Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong SAR, China.
Cells. 2020 Mar 19;9(3):756. doi: 10.3390/cells9030756.
Mesenchymal stromal/stem cells (MSCs) reside in many human tissues and comprise a heterogeneous population of cells with self-renewal and multi-lineage differentiation potential, making them useful in regenerative medicine. It remains inconclusive whether MSCs isolated from different tissue sources exhibit variations in biological features. In this study, we derived MSCs from adipose tissue (AT-MSC) and compact bone (CB-MSC). We found that early passage of MSCs was readily expandable ex vivo, whereas the prolonged culture of MSCs showed alteration of cell morphology to fibroblastoid and reduced proliferation. CB-MSCs and AT-MSCs at passage 3 were CD29, CD44, CD105, CD106, and Sca-1; however, passage 7 MSCs showed a reduction of MSC markers, indicating loss of stem cell population after prolonged culturing. Strikingly, CB-MSC was found more efficient at undergoing osteogenic differentiation, while AT-MSC was more efficient to differentiate into adipocytes. The biased differentiation pattern of MSCs from adipogenic or osteogenic tissue source was accompanied by preferential expression of the corresponding lineage marker genes. Interestingly, CB-MSCs treated with DNA demethylation agent 5-azacytidine showed enhanced osteogenic and adipogenic differentiation, whereas the treated AT-MSCs are less competent to differentiate. Our results suggest that the epigenetic state of MSCs is associated with the biased differentiation plasticity towards its tissue of origin, proposing a mechanism related to the retention of epigenetic memory. These findings facilitate the selection of optimal tissue sources of MSCs and the ex vivo expansion period for therapeutic applications.
间充质基质/干细胞（MSCs）存在于许多人体组织中，由具有自我更新和多系分化潜能的异质性细胞群体组成，使其在再生医学中具有应用价值。目前尚不清楚是否来自不同组织来源的 MSC 在生物学特征上存在差异。在这项研究中，我们从脂肪组织（AT-MSC）和密质骨（CB-MSC）中分离出 MSC。我们发现早期传代的 MSC 很容易在体外扩增，而 MSC 的长期培养会导致细胞形态向成纤维细胞样改变，并减少增殖。第 3 代 CB-MSC 和 AT-MSC 表达 CD29、CD44、CD105、CD106 和 Sca-1；然而，第 7 代 MSC 显示 MSC 标志物减少，表明长期培养后干细胞群体减少。值得注意的是，CB-MSC 更有效地向成骨细胞分化，而 AT-MSC 更有效地向脂肪细胞分化。来自脂肪组织或成骨组织的 MSC 偏向性分化模式伴随着相应谱系标记基因的优先表达。有趣的是，用 DNA 去甲基化剂 5-氮杂胞苷处理的 CB-MSC 表现出增强的成骨和成脂分化，而处理后的 AT-MSC 分化能力较弱。我们的结果表明，MSC 的表观遗传状态与其组织来源的偏向性分化可塑性有关，提出了一种与保留表观遗传记忆相关的机制。这些发现有助于选择最佳的 MSC 组织来源和治疗应用的体外扩增周期。
