Amado Luciano C, Saliaris Anastasios P, Schuleri Karl H, St John Marcus, Xie Jin-Sheng, Cattaneo Stephen, Durand Daniel J, Fitton Torin, Kuang Jin Qiang, Stewart Garrick, Lehrke Stephanie, Baumgartner William W, Martin Bradley J, Heldman Alan W, Hare Joshua M
Department of Medicine, Cardiology Division, The Johns Hopkins Hospital, Blalock 618, 600 North Wolfe Street, Baltimore, MD 21287, USA.
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9. doi: 10.1073/pnas.0504388102. Epub 2005 Aug 1.
Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction. Second, cellular transplantation resulted in long-term engraftment, profound reduction in scar formation, and near-normalization of cardiac function. Third, transplanted cells were pre-prepared from an allogeneic donor and were not rejected, a major practical advance for widespread application of this therapy. Together, these findings demonstrate that the direct injection of cellular grafts into damaged myocardium is safe and effective in the perii-nfarct period. The direct delivery of cells to necrotic myocardium offers a valuable alternative to intracoronary cell injections, and the use of allogeneic mesenchymal stem cells provides a valuable strategy for cardiac regenerative therapy that avoids the need for preparing autologous cells from the recipient.
尽管自体全骨髓用于心脏修复的临床试验显示出了有前景的结果,但关于这种治疗方法的许多实际问题和作用机制仍存在很大争议。在此,我们报告了一项对猪进行骨髓间充质干细胞随机研究的结果,该研究为细胞心肌成形术提供了一些新的见解。首先,在心肌梗死后3天,通过经皮注射导管安全地注射细胞。其次,细胞移植导致长期植入、瘢痕形成显著减少以及心脏功能接近正常化。第三,移植的细胞是从同种异体供体预先制备的,且未被排斥,这是该治疗方法广泛应用的一项重大实际进展。总之,这些发现表明,在梗死周围期将细胞移植物直接注射到受损心肌中是安全有效的。将细胞直接递送至坏死心肌为冠状动脉内细胞注射提供了一种有价值的替代方法,并且使用同种异体间充质干细胞为心脏再生治疗提供了一种有价值的策略,避免了从受体制备自体细胞的需求。