CD133 Identifies a Human Bone Marrow Stem/Progenitor Cell Sub-population With a Repertoire of Secreted Factors That Protect Against Stroke
CD133 Identifies a Human Bone Marrow Stem/Progenitor Cell Sub-population With a Repertoire of Secreted Factors That Protect Against Stroke
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DOI：
10.1038/mt.2009.185
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发表时间：
2009-11-01
影响因子：
12.4
通讯作者：
Spees, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Bakondi, Benjamin;Shimada, Issei S.;Spees, Jeffrey L.
骨髓基质细胞(BMSCs)的修复特性部分归因于分泌因子的旁分泌作用。我们通过塑料贴壁法分离出典型的人BMSCs，并将其与CD133(CD133来源的BMSCs，CD133BMSCs)或CD271[p75低亲和力神经生长因子受体(p75LNGFR，p75BMSCs)]的磁激活细胞分选法分离的BMSC亚群进行比较。表达基因芯片分析和选择的生长因子和细胞因子在常氧和低氧条件下分泌的酶联免疫吸附分析(ELISA)表明，这三个瞬时扩增的祖细胞群彼此不同。CD133BMSC条件培养液对神经前体细胞的保护作用优于p75BMSC条件培养液。心内(动脉)给予浓缩的CD133BMSC CDM可提供神经保护，并显著减少脑缺血后小鼠的皮质梗死体积。为了支持BMSC作用的旁分泌假说，与CD133 BMSC(细胞)注射的效果相比，动脉内注射CD133BMSC CDM提供了显著更好的卒中保护作用。与p75BMSCs或通常分离的BMSCs相比，CD133BMSCs的CDM也提供了更好的卒中保护作用。CD133识别成人骨髓中的非造血干/祖细胞亚群，CD133骨髓间充质干细胞CD133可能为卒中患者提供神经保护。
The reparative properties of bone marrow stromal cells (BMSCs) have been attributed in part to the paracrine action of secreted factors. We isolated typical human BMSCs by plastic adherence and compared them with BMSC sub-populations isolated by magnetic-activated cell sorting against CD133 (CD133-derived BMSCs, CD133BMSCs) or CD271 [p75 low-affinity nerve growth factor receptor (p75LNGFR), p75BMSCs]. Microarray assays of expressed genes, and enzyme-linked immunosorbent assays (ELISAs) of selected growth factors and cytokines secreted under normoxic and hypoxic conditions demonstrated that the three transit-amplifying progenitor cell populations were distinct from one another. CD133BMSC-conditioned medium (CdM) was superior to p75BMSC CdM in protecting neural progenitor cells against cell death during growth factor/nutrient withdrawal. Intracardiac (arterial) administration of concentrated CD133BMSC CdM provided neuroprotection and significantly reduced cortical infarct volumes in mice following cerebral ischemia. In support of the paracrine hypothesis for BMSC action, intra-arterial infusion of CD133BMSC CdM provided significantly greater protection against stroke compared with the effects of CD133BMSC (cell) administration. CdM from CD133BMSCs also provided superior protection against stroke compared with that conferred by CdM from p75BMSCs or typically isolated BMSCs. CD133 identifies a sub- population of nonhematopoietic stem/progenitor cells from adult human bone marrow, and CD133BMSC CdM may provide neuroprotection for patients with stroke.