Nature Biotechnology：干细胞能够帮助大鼠心脏受损后恢复

生物谷

生物谷报道：最近，研究人员宣称：人胚胎干细胞能在心脏梗塞后改善心脏功能，至少在大鼠上。由于理论上干细胞可以分化为许多种细胞，因此人干细胞被认为是一种可能治疗很多疾病和脏器损伤的潜在治疗方法。这项研究表明大鼠实验性心脏受损后，人胚胎干细胞能够用来减轻损伤并改善功能。

这项研究成果是未来干细胞能够成为治疗心脏病的主要治疗方法的有利支持。先前的研究表明来源于人胚胎干细胞的心肌细胞能够在未受损的大鼠中形成新的心肌，研究成果已发表在《Nature Biotechnology》的网络版上。但是当他们在诱发心肌梗塞大鼠上进行同样的尝试时，实验却失败了，主要是由于两个原因：第一，很难获得能产生足够心肌细胞的干细胞；第二，移植的细胞不能存活。为了克服第一个困难，研究人员将单层干细胞用两种化合物——苯丙酸诺龙A和骨形态发生蛋白4——处理，这两种物质可以增加干细胞分化为心肌细胞的比例。早先的处理方法仅能获得不到1%心肌细胞，而这种新方法能增加到30%以上。Murray博士和他的同事称，再增加一个离心的步骤就可以获得含有82.6%心肌细胞的培养基。但是他们发现，只是简单的把细胞注入到受损的心脏效果并不佳，这暗示细胞可能处于濒死的状态，可能是由于其他一些因素包括缺血、凋亡和炎症所导致的。为了阻止细胞濒死，研究人员发明一种“pro-survival cocktail”的方法，目的是阻断各种不同死亡途径。实验表明用鸡尾移植的大鼠100%的移植成功，而没用鸡尾的仅有18%移植成功。这是目前为止使用细胞修复实体组织的最成功的尝试之一，每个接受治疗的心脏都是发育良好的组织移植。”而且，与其他的对照组比接受治疗的动物在心脏病发作28天后能有一个较好心脏功能。

总之，研究表明干细胞治疗能够延缓心脏病进展，改善心脏整体功能，并增加局部心室壁运动。主要作者、华盛顿大学的Michael Laflamme博士说“我们发现移植物不仅仅是在大鼠的心脏存活——他们还能帮助改善受损心脏的功能。那是非常重要的，因为对于心肌梗塞患者来说主要问题之一是心脏是损坏的，它几乎不能泵出血液，这种治疗可以帮助心肌复原并维持功能。”

Figure 1 - Protection of hES cell–derived cardiomyocyte grafts by the pro-survival cocktail.

(a,b) Histologic analysis of graft cell survival. Heat-shocked hES cell–derived cardiomyocytes were injected into infarcted hearts of nude rats in the presence of SFM, Matrigel-only (a, Cells+Matrigel), or the full pro-survival cocktail (PSC) including Matrigel (b, Cells+PSC) (n = 5 per group). Sections were stained with an antibody to -myosin heavy chain ( MHC, red chromagen) as well as a human-specific pan-centromeric in situ hybridization probe (huCent, brown DAB deposit) to identify total human (that is, huCent+) and specifically human cardiac (that is, MHC and huCent double-positive) graft cells. The human cardiomyocytes, indicated by arrows, were significantly more abundant in histologic sections from the Cells+PSC group than in Cells+Matrigel alone group. Histology is not depicted from the recipients of cells in SFM alone because none of these hearts showed even a single surviving human nucleus after 1 week. Counterstain, fast green; scale bar, 50 m. (c) Quantification of hES cell–derived cardiomyocyte graft size. Although no grafts were detected in any rats receiving hES cell–derived cardiomyocytes delivered in SFM alone (Cells+SFM), all rats receiving cells delivered in Matrigel-only (Cells+Matrigel) or in the full prosurvival cocktail (Cells+PSC) showed surviving graft (5/5 rats per group). However, recipients of cells in the full prosurvival cocktail (Cells+PSC) showed a mean of approximately fourfold more -myosin-positive graft cells than did the Matrigel-only group. Note that counts indicate the total number of cells observed on sampled sections, not the total number of cells per heart. ^*, P < 0.05.

作者简介：

Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts

Michael A Laflamme, Kent Y Chen, Anna V Naumova, Veronica Muskheli, James A Fugate, Sarah K Dupras, Hans Reinecke, Chunhui Xu, Mohammad Hassanipour, Shailaja Police, Chris O'Sullivan, Lila Collins, Yinhong Chen, Elina Minami, Edward A Gill, Shuichi Ueno, Chun Yuan, Joseph Gold & Charles E Murry

Published online: 26 August 2007; | doi:10.1038/nbt1327

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