Fedak Paul W M
Division of Cardiac Surgery, Department of Cardiac Sciences and Surgery, University of Calgary, Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.
Semin Thorac Cardiovasc Surg. 2008 Summer;20(2):87-93. doi: 10.1053/j.semtcvs.2008.04.001.
Structural ventricular remodeling determines the clinical progression of heart failure and has emerged as an important target for the development of novel medical and surgical therapeutic strategies. Cell transplantation is an innovative biologic therapy that may restore myocardial structure and function in failing hearts. With current forms of cell transplant therapy, true myocardial regeneration has been limited. However, cell transplantation can predictably limit maladaptive ventricular remodeling through multiple synergistic paracrine mechanisms. Some of the paracrine factors released by transplanted cells have been defined. These paracrine signals may provide beneficial effects by stimulating angiogenesis, limiting matrix disruption, and preventing apoptosis. In addition, cell transplantation may induce mobilization and homing of endogenous repair cells to injured myocardium through paracrine signals. Paracrine mediators released from transplanted cells work through multiple, diverse, and interrelated molecular pathways resulting in synergistic effects on the remodeling process. Although true myocardial regeneration remains the ultimate goal of cell therapy, the anti-remodeling abilities of cell transplantation can be harnessed to complement our contemporary surgical approaches for patients with myocardial injury at risk of congestive heart failure.
心室结构重塑决定了心力衰竭的临床进展，并已成为新型药物和手术治疗策略开发的重要靶点。细胞移植是一种创新的生物疗法，可能恢复衰竭心脏的心肌结构和功能。就目前的细胞移植治疗形式而言，真正的心肌再生一直很有限。然而，细胞移植可以通过多种协同旁分泌机制可预测地限制适应性不良的心室重塑。已确定了一些移植细胞释放的旁分泌因子。这些旁分泌信号可能通过刺激血管生成、限制基质破坏和防止细胞凋亡而产生有益作用。此外，细胞移植可能通过旁分泌信号诱导内源性修复细胞向受损心肌动员和归巢。移植细胞释放的旁分泌介质通过多种、多样且相互关联的分子途径发挥作用，从而对重塑过程产生协同效应。尽管真正的心肌再生仍然是细胞治疗的最终目标，但细胞移植的抗重塑能力可用于补充我们目前针对有充血性心力衰竭风险的心肌损伤患者的手术方法。
