Human Non-Hematopoietic CD271(pos)/CD140a(low/neg) Bone Marrow Stroma Cells Fulfill Stringent Stem Cell Criteria in Serial Transplantations.

Human Non-Hematopoietic CD271(pos)/CD140a(low/neg) Bone Marrow Stroma Cells Fulfill Stringent Stem Cell Criteria in Serial Transplantations.
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DOI:
10.1089/scd.2016.0169
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发表时间:
2016-11-01
影响因子:
4
通讯作者:
Scheding S
Scheding S
中科院分区:
医学3区
文献类型:
--
作者:
Ghazanfari R;Li H;Zacharaki D;Lim HC;Scheding S

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人骨髓含有非造血基质干/祖细胞(BMSC)群体,其在骨髓基质和造血微环境中起核心作用。然而,确切的特征和潜在的干细胞特性的定义BMSC人口尚未得到彻底的调查。使用标准的贴壁集落形成单位成纤维细胞(CFU-F)测定,我们以前已经表明,BMSC高度富集在非造血CD 271阳性/CD 140低/阴性部分的正常成人骨髓。在这项研究中,我们表明,前瞻性分离的CD 271 pos/CD 140 low/neg BMSCs表达高水平的造血支持基因和签名间充质和多能性基因在单细胞的基础上。此外,CD 271 pos/CD 140 low/neg BMSCs产生具有典型表面标志物特征和三系分化潜能的非粘附球集落(间质球)。重要的是,将CD 271 pos/CD 140 low/neg BMSC衍生的间充质球(单细胞和散装)连续移植到免疫缺陷NOD scid gamma(NSG)小鼠中,在初次和二次移植后均显示出间充质球数量增加和完全分化潜力。相反,在标准贴壁培养条件下,BMSC自我更新潜力下降。因此,这些数据表明,CD 271 pos/CD 140 low/neg BMSCs代表了具有MSC表型和球体形成能力的原代干细胞群体,其在连续移植环境中满足严格的体内功能性干细胞标准。
Human bone marrow contains a population of non-hematopoietic stromal stem/progenitor cells (BMSCs), which play a central role for bone marrow stroma and the hematopoietic microenvironment. However, the precise characteristics and potential stem cell properties of defined BMSC populations have not yet been thoroughly investigated. Using standard adherent colony-forming unit fibroblast (CFU-F) assays, we have previously shown that BMSCs were highly enriched in the nonhematopoietic CD271pos/CD140alow/neg fraction of normal adult human bone marrow. In this study, we demonstrate that prospectively isolated CD271pos/CD140alow/neg BMSCs expressed high levels of hematopoiesis supporting genes and signature mesenchymal and multipotency genes on a single cell basis. Furthermore, CD271pos/CD140alow/neg BMSCs gave rise to non-adherent sphere colonies (mesenspheres) with typical surface marker profile and trilineage in vitro differentiation potential. Importantly, serial transplantations of CD271pos/CD140alow/neg BMSC-derived mesenspheres (single cell and bulk) into immunodeficient NOD scid gamma (NSG) mice showed increased mesensphere numbers and full differentiation potential after both primary and secondary transplantations. In contrast, BMSC self-renewal potential decreased under standard adherent culture conditions. These data therefore indicate that CD271pos/CD140alow/neg BMSCs represent a population of primary stem cells with MSC phenotype and sphere-forming capacity that fulfill stringent functional stem cell criteria in vivo in a serial transplantation setting.
DOI: 10.1016/j.cell.2007.08.025
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