Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
Biomaterials. 2012 Feb;33(5):1303-14. doi: 10.1016/j.biomaterials.2011.10.019. Epub 2011 Nov 10.
Stem cell transplantation has been suggested as a treatment for myocardial infarction, but clinical studies have yet to demonstrate conclusive, positive effects. This may be related to poor survival of the transplanted stem cells due to the inflammatory response following myocardial infarction. To address this, a scaffold-based stem cell delivery system was functionalised with anti-inflammatory plasmids (interleukin-10) to improve stem cell retention and recovery of cardiac function. Myocardial infarction was induced and these functionalised scaffolds were applied over the infarcted myocardium. Four weeks later, stem cell retention, cardiac function, remodelling and inflammation were quantified. Interleukin-10 gene transfer improved stem cell retention by more than five-fold and the hearts treated with scaffold, stem cells and interleukin-10 had significant functional recovery compared to the scaffold control (scaffold: -10 ± 7%, scaffold, interleukin-10 and stem cells: +7 ± 6%). This improved function was associated with increased infarcted wall thickness and increased ratios of collagen type III/type I, decreased cell death, and a change in macrophage markers from mainly cytotoxic in the scaffold group to mainly regulatory in scaffold, stem cells and interleukin-10 group. Thus, treatment of myocardial infarction with stem cells and interleukin-10 gene transfer significantly improved stem cell retention and ultimately improved overall cardiac function.
干细胞移植被提议作为心肌梗死的一种治疗方法，但临床研究尚未证明其具有明确的积极效果。这可能与心肌梗死后炎症反应导致移植的干细胞存活率低有关。为了解决这个问题，一种基于支架的干细胞输送系统被用具有抗炎作用的质粒（白细胞介素-10）进行了功能化修饰，以提高干细胞的保留率和心脏功能的恢复。诱导心肌梗死，并将这些功能化支架应用于梗死的心肌上。四周后，对干细胞的保留率、心脏功能、重塑和炎症进行了定量分析。白细胞介素-10 基因转移将干细胞的保留率提高了五倍以上，与支架对照组相比，用支架、干细胞和白细胞介素-10 治疗的心脏具有显著的功能恢复（支架：-10±7%，支架、白细胞介素-10 和干细胞：+7±6%）。这种功能的改善与梗死壁厚度的增加以及胶原 III/胶原 I 比值的增加、细胞死亡的减少以及巨噬细胞标志物的变化有关，在支架组中，巨噬细胞标志物主要是细胞毒性的，而在支架、干细胞和白细胞介素-10 组中则主要是调节性的。因此，用干细胞和白细胞介素-10 基因转移治疗心肌梗死显著提高了干细胞的保留率，并最终改善了整体心脏功能。
