Therapeutic effects of human STRO-3-selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia.
Therapeutic effects of human STRO-3-selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia.
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DOI：
10.1111/j.1582-4934.2010.01241.x
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发表时间：
2011-10
影响因子：
5.3
通讯作者：
Itescu S
中科院分区：
文献类型：
--
作者：
See F;Seki T;Psaltis PJ;Sondermeijer HP;Gronthos S;Zannettino AC;Govaert KM;Schuster MD;Kurlansky PA;Kelly DJ;Krum H;Itescu S
基质前体抗原(Stro)-3已被证实可识别成人骨髓(BM)来源的间充质祖细胞亚群，可能具有心脏保护作用。我们试图就Stro-3免疫选择和培养扩增的间充质前体细胞(MPC)在心肌缺血中的生物学和治疗潜力进行表征。从未分离的骨髓单个核细胞(MNC)中免疫选择富含成纤维细胞集落形成单位的Stro-3+MPC。与传统的塑料贴壁法分离的间充质干细胞相比，MPC在培养扩增过程中表现出更强的增殖能力，表达更高水平的早期干细胞标志物以及各种促血管生成和心脏保护的细胞因子，并显示出更高的三倍体发育效率。心肌梗死(MI)大鼠心肌内注射MPC可促进左心室恢复，抑制左心室扩大。这些有益的作用与组织水平上的心脏保护和促血管生成作用有关，尽管细胞植入率很低。心肌梗死大鼠经MPC条件培养液(CM)处理后，左心功能和大小保持不变，心肌细胞凋亡和纤维化减少，新生血管增多，既涉及驻留的血管细胞，也涉及循环内皮祖细胞(EPC)。CM图谱显示了多种心脏保护和促血管生成因子，它们在培养的心肌细胞、组织驻留的血管细胞和内皮祖细胞中具有生物活性。从骨髓单个核细胞中免疫选择Stro-3+MPC在体外扩增过程中维持未成熟MPC的数量方面具有优势。将培养扩增的MPC移植到心肌梗死后心脏可产生治疗效果，至少部分归因于旁分泌作用机制。因此，MPC是一种很有前途的治疗心肌缺血的方法。
Stromal precursor antigen (STRO)-3 has previously been shown to identify a subset of adult human bone marrow (BM)-derived mesenchymal lineage precursors, which may have cardioprotective potential. We sought to characterize STRO-3-immunoselected and culture-expanded mesenchymal precursor cells (MPCs) with respect to their biology and therapeutic potential in myocardial ischemia. Immunoselection of STRO-3+ MPCs enriched for fibroblastic colony forming units from unfractionated BM mononuclear cells (MNCs). Compared to mesenchymal stem cells conventionally isolated by plastic adherence, MPCs demonstrated increased proliferative capacity during culture expansion, expressed higher levels of early ‘stem cell’ markers and various pro-angiogenic and cardioprotective cytokines, and exhibited greater trilineage developmental efficiency. Intramyocardial injection of MPCs into a rat model of myocardial infarction (MI) promoted left ventricular recovery and inhibited left ventricular dilatation. These beneficial effects were associated with cardioprotective and pro-angiogenic effects at the tissue level, despite poor engraftment of cells. Treatment of MI rats with MPC-conditioned medium (CM) preserved left ventricular function and dimensions, reduced myocyte apoptosis and fibrosis, and augmented neovascularization, involving both resident vascular cells and circulating endothelial progenitor cells (EPCs). Profiling of CM revealed various cardioprotective and pro-angiogenic factors, which had biological activity in cultures of myocytes, tissue-resident vascular cells and EPCs. Prospective immunoselection of STRO-3+ MPCs from BM MNCs conferred advantage in maintaining a population of immature MPCs during ex vivo expansion. Transplantation of culture-expanded MPCs into the post-MI heart resulted in therapeutic benefit, attributable at least in part to paracrine mechanisms of action. Thus, MPCs represent a promising therapy for myocardial ischemia.
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影响因子：
6.2
作者：
Shui, CX;Spelsberg, TC;Khosla, S
通讯作者：
Khosla, S
影响因子：
4
作者：
Gronthos, S;Zannettino, ACW;Simmons, PJ
通讯作者：
Simmons, PJ
影响因子：
37.8
作者：
Dixon JA;Gorman RC;Stroud RE;Bouges S;Hirotsugu H;Gorman JH 3rd;Martens TP;Itescu S;Schuster MD;Plappert T;St John-Sutton MG;Spinale FG
通讯作者：
Spinale FG
影响因子：
20.1
作者：
Huang J;Zhang Z;Guo J;Ni A;Deb A;Zhang L;Mirotsou M;Pratt RE;Dzau VJ
通讯作者：
Dzau VJ
影响因子：
6.2
作者：
Shi, S;Gronthos, S
通讯作者：
Gronthos, S