Department Anatomy, Histology & Forensic Medicine, University of Florence, Viale G.B.Morgagni, 85, I-50134 Florence, Italy.
Curr Pharm Des. 2010;16(8):915-28. doi: 10.2174/138161210790883390.
Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells in basic research and clinical trials of cell based therapy for cardiac repair and regeneration. Although SkMB engraftment into the post-infarcted heart has been consistently found to improve cardiac contractile function, the underlying therapeutic mechanisms remain still a matter of controversy and debate. This is basically because SkMBs do not attain a cardiac-like phenotype once homed into the diseased heart nor they form a contractile tissue functionally coupled with the surrounding viable myocardium. This issue of concern has generated the idea that the cardiotropic action of SkMBs may depend on the release of paracrine factors. However, the paracrine hypothesis still remains ill-defined, particularly concerning the identification of the whole spectrum of cell-derived soluble factors and details on their cardiac effects. In this context, the possibility to genetically engineering SkMBs to potentate their paracrine attitudes appears particularly attractive and is actually raising great expectation. Aim of the present review is not to cover all the aspects of cell-based therapy with SkMBs, as this has been the object of previous exhaustive reviews in this field. Rather, we focused on novel aspects underlying the interactions between SkMBs and the host cardiac tissues which may be relevant for directing the future basic and applied research on SkMB transplantation for post ischemic cardiac dysfunction.
直到最近,骨骼肌母细胞(SkMB)一直是基础研究和细胞治疗临床试验中应用最广泛的细胞,用于心脏修复和再生。尽管 SkMB 植入梗死后的心脏一直被发现可以改善心脏收缩功能,但潜在的治疗机制仍然存在争议。这主要是因为 SkMB 一旦归巢到患病的心脏,就不会获得类似于心脏的表型,也不会形成与周围存活心肌功能偶联的收缩组织。这一令人关注的问题引发了这样一种观点,即 SkMB 的心脏趋向性作用可能取决于旁分泌因子的释放。然而,旁分泌假说仍然定义不明确,特别是关于确定细胞来源的可溶性因子的整个范围及其对心脏的影响的细节。在这种情况下,对 SkMB 进行基因工程改造以增强其旁分泌作用的可能性似乎特别有吸引力,并且确实引起了人们的极大期望。本综述的目的不是涵盖 SkMB 细胞治疗的所有方面,因为这是该领域之前详尽综述的对象。相反,我们专注于 SkMB 与宿主心脏组织之间相互作用的新方面,这可能与指导 SkMB 移植治疗缺血后心脏功能障碍的未来基础和应用研究相关。