近日,以色列科学家宣布,日前他们成功将取自老年心脏衰竭患者的皮肤细胞转化成了健康的心肌细胞。这些细胞已被证明能够发育成健康的心肌组织,并通过了大鼠移植实验的验证,类似疗法有望10年内在临床上获得应用。相关论文发表在5月23日出版的《欧洲心脏期刊》(European Heart Journal )上。
负责该研究的以色列技术研究所研究员利奥尔·格普斯顿说,实验表明完全可以将采自心脏衰竭老年患者的皮肤细胞培育成健康的心肌细胞,而这种新培育出的心肌细胞几乎和患者刚出生时的心肌细胞无异,该疗法未来有望成为拯救心脏病患者的重要手段。
心脏衰竭是由心肌受损所引起的一种疾病,患病后心脏无法正常泵出足够的血液来供应身体各个器官活动及代谢的需求,逐步失去心脏功能,该症是导致65岁以上老年人入院的主要原因,近年来发病更为普遍。目前,对于严重心脏衰竭患者只能依靠机械设备或寄希望于心脏移植。
此次研究中,格普斯顿的团队首先从两名年龄分别是51岁和61岁的男性心脏衰竭患者身上获取皮肤细胞,然后通过向皮肤细胞中添加3个基因和一种名为丙戊酸的小分子的方式将其转化为诱导多能干细胞,最后再培育成心肌细胞。研究人员发现,这些由老年心脏衰竭患者的皮肤细胞培育成的心肌细胞和那些由健康的年轻志愿者提供的皮肤细胞培育成的心肌细胞一样有效。而后研究人员在实验室中将心肌细胞与现有的心脏组织放在一起进行培养,结果发现24到48小时内,两种类型的组织就能够一起跳动。之后,新组织被移植到健康大鼠的心脏,很快便与大鼠细胞建立连接。
格普斯顿说,在将这些组织移植到人体之前还需经过许多测试和完善,因此该疗法数年后才能在临床上获得应用。但实验证明了用患者自体细胞治疗心脏病的梦想完全能够实现。
伦敦大学心血管病学教授约翰·马丁说,这是一项有趣的工作,有望成为一种有效的疗法,但在实际应用前还有很多事情要做。英国爱丁堡大学心脏病专家尼古拉斯·米尔斯说,虽然该疗法在用于临床前还需要进一步完善和细化,但结果还是令人鼓舞,它代表着我们距有效修复心脏这一梦想又近了一步。(生物谷Bioon.com)
doi:10.1093/eurheartj/ehs096
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Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients
Limor Zwi-Dantsis1,2, Irit Huber1, Manhal Habib1, Aaron Winterstern1, Amira Gepstein1, Gil Arbel1 and Lior Gepstein1,3,*
Aims Myocardial cell replacement therapies are hampered by a paucity of sources for human cardiomyocytes and by the expected immune rejection of allogeneic cell grafts. The ability to derive patient-specific human-induced pluripotent stem cells (hiPSCs) may provide a solution to these challenges. We aimed to derive hiPSCs from heart failure (HF) patients, to induce their cardiomyocyte differentiation, to characterize the generated hiPSC-derived cardiomyocytes (hiPSC-CMs), and to evaluate their ability to integrate with pre-existing cardiac tissue. Methods and results Dermal fibroblasts from two HF patients were reprogrammed by retroviral delivery of Oct4, Sox2, and Klf4 or by using an excisable polycistronic lentiviral vector. The resulting HF-hiPSCs displayed adequate reprogramming properties and could be induced to differentiate into cardiomyocytes with the same efficiency as control hiPSCs (derived from human foreskin fibroblasts). Gene expression and immunostaining studies confirmed the cardiomyocyte phenotype of the differentiating HF-hiPSC-CMs. Multi-electrode array recordings revealed the development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation. Next, functional integration and synchronized electrical activities were demonstrated between hiPSC-CMs and neonatal rat cardiomyocytes in co-culture studies. Finally, in vivo transplantation studies in the rat heart revealed the ability of the HF-hiPSC-CMs to engraft, survive, and structurally integrate with host cardiomyocytes. Conclusions Human-induced pluripotent stem cells can be established from patients with advanced heart failure and coaxed to differentiate into cardiomyocytes, which can integrate with host cardiac tissue. This novel source for patient-specific heart cells may bring a unique value to the emerging field of cardiac regenerative medicine.