Stem Cell Biology Department, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
Indian J Med Res. 2013 Feb;137(2):270-82.
Cell based regenerative therapy has emerged as one of the most promising options of treatment for patients suffering from heart failure. Various adult stem cells types have undergone extensive clinical trials with limited success which is believed to be more of a cytokine effect rather than cell therapy. Pluripotent human embryonic stem cells (hESCs) have emerged as an attractive candidate stem cell source for obtaining cardiomyocytes (CMs) because of their tremendous capacity for expansion and unquestioned potential to differentiate into CMs. Studies carried out in animal models indicate that ES-derived CMs can partially remuscularize infarcted hearts and improve contractile function; however, the effect was not sustained over long follow up periods due to their limited capacity of cell division in vivo. Thus, the concept of transplanting multipotent cardiovascular progenitors derived from ES cells has emerged since the progenitors retain robust proliferative ability and multipotent nature enabling repopulation of other myocardial elements also in addition to CMs. Transplantation of CMs (progenitors) seeded in biodegradable scaffold and gel based engineered constructs has met with modest success due to issues like cell penetration, nutrient and oxygen availability and inflammation triggered during scaffold degradation inversely affecting the seeded cells. Recently cell sheet based tissue engineering involving culturing cells on 'intelligent' polymers has been evolved. Generation of a 3-D pulsatile myocardial tissue has been achieved. However, these advances have to be looked at with cautious optimism as many challenges need to be overcome before using these in clinical practice.
基于细胞的再生疗法已成为治疗心力衰竭患者最有前途的治疗选择之一。各种成体干细胞类型已经进行了广泛的临床试验,但收效甚微,这被认为更多的是细胞因子的作用,而不是细胞治疗。多能人胚胎干细胞(hESCs)因其具有巨大的扩增能力和无可置疑的分化为心肌细胞(CMs)的潜力,已成为获得心肌细胞的有吸引力的候选干细胞来源。在动物模型中进行的研究表明,ES 衍生的 CMs 可以部分重塑梗死的心脏并改善收缩功能;然而,由于其在体内分裂的能力有限,这种效果在长时间的随访中并没有持续。因此,源于 ES 细胞的多能心血管祖细胞的移植概念已经出现,因为祖细胞保留了强大的增殖能力和多能性,除了 CMs 之外,还能够重新填充其他心肌成分。将种子细胞接种在可生物降解的支架和基于凝胶的工程构建体中的 CMs(祖细胞)的移植已经取得了一定的成功,但由于细胞穿透、营养和氧气供应以及支架降解过程中引发的炎症等问题,导致种子细胞的存活率较低。最近,涉及在“智能”聚合物上培养细胞的基于细胞片层的组织工程已经得到发展。已经实现了 3-D 搏动性心肌组织的生成。然而,在将这些方法应用于临床实践之前,还需要谨慎乐观地看待这些进展,因为还需要克服许多挑战。
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