Mosna Federico, Annunziato Francesco, Pizzolo Giovanni, Krampera Mauro
Stem Cell Research Laboratory, Section of Hematology, Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy.
Cardiovasc Hematol Agents Med Chem. 2010 Oct 1;8(4):227-43. doi: 10.2174/187152510792481216.
In the last decade several attempts have been made to achieve the goal of cardiac regeneration after myocardial infarction. To date, two cell types have completed phase-III clinical trials: Skeletal Myoblasts and Bone-Marrow Mononuclear Cells (BM-MNCs). In the first case, all benefits have been limited by an increased risk of arrhythmia. In the case of BM-cells, most studies showed a significant, although limited, advantage in the cell-treated group. This may be due to the choice of the wrong BM cell type: other candidates would be e.g. CD34(+) HSCs, or non-hematopoietic Mesenchymal Stem Cells. After positive results from the experimental studies, phase I/II clinical trials are currently on-going for both. Ideally, the best cell to use to regenerate the heart would be a precursor of all cardiac lineages; until the isolation and expansion of Cardiac Stem Cells (CSCs), such a cell was thought to exist only during embryogenesis. Using CSCs researchers managed to generate electrically-coupled contractile tissue within the infarct of animal models. Still, some doubts persist over the possibility to translate such results in real-life patients. Another approach, therefore, involves the use of induced Pluripotent Stem Cells (iPS) obtained from fibroblasts after genetic reprogramming. This new type of cell would combine the pluripotency of embryonal stem cells with the advantages of an autologous use. Nevertheless, iPS cells form teratomas, and their effective differentiation in vivo is largely unknown. This review will critically compare the data from the Literature concerning cell therapy after myocardial infarction. Can we name the best cell?
在过去十年中，人们为实现心肌梗死后心脏再生的目标进行了多次尝试。迄今为止，有两种细胞类型已完成III期临床试验：骨骼肌成肌细胞和骨髓单个核细胞（BM-MNCs）。在第一种情况下，所有益处都因心律失常风险增加而受到限制。对于BM细胞，大多数研究表明，细胞治疗组虽有显著但有限的优势。这可能是由于选择了错误的BM细胞类型：其他候选细胞例如CD34(+)造血干细胞或非造血间充质干细胞。在实验研究取得阳性结果后，目前这两种细胞的I/II期临床试验正在进行。理想情况下，用于心脏再生的最佳细胞应该是所有心脏谱系的前体细胞；在心脏干细胞（CSCs）被分离和扩增之前，人们认为这种细胞只在胚胎发育过程中存在。利用CSCs，研究人员成功在动物模型梗死区内生成了电耦合收缩组织。然而，对于能否将这些结果应用于实际患者仍存在一些疑问。因此，另一种方法涉及使用经基因重编程从成纤维细胞获得的诱导多能干细胞（iPS）。这种新型细胞将胚胎干细胞的多能性与自体使用的优势结合起来。然而，iPS细胞会形成畸胎瘤，其在体内的有效分化情况很大程度上尚不清楚。本综述将批判性地比较文献中有关心肌梗死后细胞治疗的数据。我们能确定最佳细胞吗？
