Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.
Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.
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DOI：
10.1161/circresaha.110.222703
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发表时间：
2010-10-01
影响因子：
20.1
通讯作者：
Hare JM
中科院分区：
文献类型：
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作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
心脏的再生潜力不足以在损伤后完全恢复功能心肌，这促使人们寻求基于细胞的替代策略。骨髓间充质干细胞（MSC）具有心脏修复的能力，似乎超过了它们向心肌细胞分化的能力。在这里，我们验证了骨髓来源的MSCs刺激内源性心脏干细胞（CSCs）的增殖和分化作为其再生库的一部分的假设。31头雌性约克郡猪实验性心肌梗死（MI）；3天后接受经心内膜注射同种异体男性骨髓来源的间充质干细胞、MSC浓缩条件培养基（CCM）或安慰剂（Plasmalyte）。另设不注射对照组。骨髓间充质干细胞移植分化为心肌细胞和血管结构。此外，内源性c-kit+ CSCs在MSC处理的动物中比对照组增加了20倍（p<0.001）， GATA-4+ CSCs在MSC中比对照组增加了6倍（p<0.001），有丝分裂肌细胞增加了4倍。在有无MSC饲喂层的情况下，采集猪心内膜活组织切片并进行器官型培养。在体外，MSCs刺激c-kit+ CSCs向表达Nkx2-5和肌钙蛋白i的成人成心细胞增殖，MSCs刺激宿主CSCs，这是成功的基于细胞的治疗的一种新的作用机制。
The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow derived mesenchymal stem cells (MSC) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. Here we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. Female Yorkshire pigs (n=31) underwent experimental myocardial Infarction (MI); and 3 days later received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit+ CSCs increased 20-fold in MSC treated animals vs. controls (p<0.001), there was a 6-fold increase in GATA-4+ CSCs in MSC vs. control (p<0.001), and mitotic myocytes increased 4-fold. Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit+ CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I. MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.