Krause Korff, Schneider Carsten, Jaquet Kai, Kuck Karl-Heinz
Hanseatic Heart Center Hamburg, Department of Cardiology, Asklepios Hospital St. Georg, Hamburg, Germany.
Stem Cells Cloning. 2010 Mar 26;3:49-56. doi: 10.2147/sccaa.s5867.
The recent identification of bone marrow-derived adult stem cells and other types of stem cells that could improve heart function after transplantation have raised high expectations. The basic mechanisms have been studied mostly in murine models. However, these experiments revealed controversial results on transdifferentiation vs transfusion of adult stem cells vs paracrine effects of these cells, which is still being debated. Moreover, the reproducibility of these results in precisely translated large animal models is still less well investigated. Despite these weaknesses results of several clinical trials including several hundreds of patients with ischemic heart disease have been published. However, there are no solid data showing that any of these approaches can regenerate human myocardium. Even the effectiveness of cell therapy in these approaches is doubtful. In future we need in this important field of regenerative medicine: i) more experimental data in large animals that are closer to the anatomy and physiology of humans, including data on dose effects, comparison of different cell types and different delivery routes; ii) a better understanding of the molecular mechanisms involved in the fate of transplanted cells; iii) more intensive research on genuine regenerative medicine, applying genetic regulation and cell engineering.
近期骨髓来源的成体干细胞以及其他类型干细胞在移植后可改善心脏功能的发现,引发了人们很高的期望。其基本机制大多在小鼠模型中进行了研究。然而,这些实验在成体干细胞的转分化与转输以及这些细胞的旁分泌效应方面得出了有争议的结果,对此仍在争论中。此外,这些结果在精确翻译的大型动物模型中的可重复性仍较少得到研究。尽管存在这些不足,但包括数百名缺血性心脏病患者的多项临床试验结果已经发表。然而,没有确凿数据表明这些方法中的任何一种能够使人类心肌再生。甚至这些方法中细胞治疗的有效性也值得怀疑。未来,在这个再生医学的重要领域,我们需要:i)在更接近人类解剖学和生理学的大型动物中获得更多实验数据,包括剂量效应数据、不同细胞类型和不同给药途径的比较;ii)更好地理解移植细胞命运所涉及的分子机制;iii)对应用基因调控和细胞工程的真正再生医学进行更深入的研究。