Stem Cell Biology Department, National Institute for Research in Reproductive Health, Parel, Mumbai, India.
Stem Cells Dev. 2012 Jan;21(1):1-6. doi: 10.1089/scd.2011.0311. Epub 2011 Aug 29.
Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow (BM) processing for autologus stem cell therapy mainly because of their small size. The present study was conducted on human umbilical cord blood (UCB, n=6) and discarded red blood cells (RBC) fraction obtained after separation of mononuclear cells from human BM (n=6), to test this hypothesis. The results show that VSELs, which are pluripotent stem cells with maximum regenerative potential, settle along with the RBCs during Ficoll-Hypaque density separation. These cells are very small in size (3-5 μm), have high nucleo-cytoplasmic ratio, and express nuclear Oct-4, cell surface protein SSEA-4, and other pluripotent markers such as Nanog, Sox-2, Rex-1, and Tert as indicated by immunolocalization and quantitative polymerase chain reaction (Q-PCR) studies. Interestingly, a distinct population of slightly larger, round hematopoietic stem cells (HSCs) with cytoplasmic Oct-4 were detected in the "buffy" coat, which usually gets banked or used during autologus stem cell therapy. Immunohistochemical studies on the umbilical cord tissue (UCT) sections (n=3) showed the presence of nuclear Oct-4-positive VSELs and many fibroblast-like mesenchymal stem cells (MSCs) with cytoplasmic Oct-4. These VSELs with nuclear Oct-4, detected in UCB, UCT, and discarded RBC fraction obtained after BM processing, may persist throughout life, maintain tissue homeostasis, and undergo asymmetric cell division to self-renew as well as produce larger progenitor stem cells, viz. HSCs or MSCs, which follow differentiation trajectories depending on the somatic niche. Hence, it can be concluded that the true stem cells in adult body tissues are the VSELs, whereas the HSCs and MSCs are actually progenitor stem cells that arise by asymmetric cell division of VSELs. The results of the present study may help explain low efficacy reported during adult autologous stem cell trials, wherein unknowingly progenitor stem cells are injected rather than the pluripotent stem cells with maximum regenerative potential.
非常小的胚胎样干细胞（VSELs）在脐带血库和骨髓（BM）处理过程中可能会丢失，主要是因为它们的体积小。本研究对人类脐带血（UCB，n=6）和从人类 BM 分离单核细胞后获得的废弃红细胞（RBC）部分（n=6）进行了测试，以验证这一假设。结果表明，具有最大再生潜力的多能干细胞 VSELs 在 Ficoll-Hypaque 密度分离过程中与 RBC 一起沉降。这些细胞体积非常小（3-5μm），具有高核质比，并表达核 Oct-4、细胞表面蛋白 SSEA-4 以及其他多能标志物，如 Nanog、Sox-2、Rex-1 和 Tert，如免疫定位和定量聚合酶链反应（Q-PCR）研究所示。有趣的是，在“buffy”涂层中检测到了一种稍大的、圆形的造血干细胞（HSCs），细胞质中存在 Oct-4，这些 HSCs 通常在自体干细胞治疗中被储存或使用。对脐带组织（UCT）切片（n=3）的免疫组织化学研究表明，存在核 Oct-4 阳性的 VSELs 和许多具有细胞质 Oct-4 的成纤维样间充质干细胞（MSCs）。在 UCB、UCT 和 BM 处理后获得的废弃 RBC 部分中检测到的具有核 Oct-4 的这些 VSELs，可能会在整个生命周期中存在，维持组织内稳态，并通过不对称细胞分裂自我更新，以及产生更大的祖细胞干细胞，即 HSCs 或 MSCs，这些细胞根据体细胞生态位遵循不同的分化轨迹。因此，可以得出结论，成人组织中的真正干细胞是 VSELs，而 HSCs 和 MSCs 实际上是由 VSELs 不对称细胞分裂产生的祖细胞干细胞。本研究的结果可能有助于解释成人自体干细胞试验中报道的低疗效，其中无意识地注射的是祖细胞干细胞，而不是具有最大再生潜力的多能干细胞。
Expert Opin Ther Pat. 2010-8
Acta Med Croatica. 2006-6
Cells. 2021-6-28
Stem Cell Rev Rep. 2021-10
Stem Cell Res Ther. 2021-1-21
J Ovarian Res. 2020-4-17
J Cell Mol Med. 2018-4-20
Zotero 插件