Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function
Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function
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DOI：
10.1161/01.res.0000020861.20064.7e
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发表时间：
2002-05-31
影响因子：
20.1
通讯作者：
Rafii, S
中科院分区：
文献类型：
--
作者：
Edelberg, JM;Tang, LL;Rafii, S
年轻骨髓源性干细胞的输送为恢复受损的衰老心脏血管生成功能提供了一种新方法，这种功能可能是老年人缺血性心脏病相关发病率和死亡率增加的基础。最近，我们报道了老化心脏内皮细胞的改变导致心肌细胞血小板衍生生长因子(PDGF)- b诱导的旁分泌途径的失调，这有助于心脏血管生成功能受损。基于这些结果，我们假设骨髓来源的内皮前体细胞（EPCs）对PDGF通路的细胞修复可以逆转与衰老相关的血管生成活性下降。体外研究显示，幼鼠（3月龄）骨髓来源的EPCs再现了心肌细胞诱导的PDGF-B表达，而来自衰老小鼠（18月龄）骨髓的EPCs在心肌细胞存在下培养时不表达PDGF-B。将年轻的，而不是年老的，遗传标记的同基因骨髓细胞移植到完整的，未辐照的衰老小鼠中，这些小鼠将内源性衰老小鼠骨髓植入随后移植的同基因新生儿心肌的新生血管中。此外，年轻骨髓来源的EPCs恢复了衰老宿主血管生成PDGF-B诱导途径和心脏血管生成。同种异体心脏移植存活率：3月龄对照组，8/8；18月龄对照组，1/8；18月龄供者接受3月龄小鼠骨髓，15/16；或18月龄小鼠，0/6
Delivery of young bone marrow-derived stem cells offers a novel approach for restoring the impaired senescent cardiac angiogenic function that may underlie the increased morbidity and mortality associated with ischemic heart disease in older individuals. Recently, we reported that alterations in endothelial cells of the aging heart lead to a dysregulation in the cardiac myocyte platelet-derived growth factor (PDGF)-B-induced paracrine pathway, which contributes to impaired cardiac angiogenic function. Based on these results, we hypothesized that cellular restoration of the PDGF pathway by bone marrow-derived endothelial precursor cells (EPCs) could reverse the aging-associated decline in angiogenic activity. In vitro studies revealed that young murine (3-month-old) bone marrow-derived EPCs recapitulated the cardiac myocyte-induced expression of PDGF-B, whereas EPCs from the bone marrow of aging mice (18-month-old) did not express PDGF-B when cultured in the presence of cardiac myocytes. Transplantation of young, but not old, genetically marked syngeneic bone marrow cells into intact, unirradiated aging mice that populated the endogenous senescent murine bone marrow incorporated into the neovasculature of subsequently transplanted syngeneic neonatal myocardium, Moreover, the young bone marrow-derived EPCs restored the senescent host angiogenic PDGF-B induction pathway and cardiac angiogenesis, with graft survival and myocardial activity in the aging murine host (cardiac allograft viability: 3-month-old controls, 8/8; 18-month-old controls, 1/8; 18-month-old donors receiving bone marrow from 3-month-old mice, 15/16; or 18-month-old mice, 0/6; P