Aging impairs the angiogenic response to ischemic injury and the activity of implanted cells: combined consequences for cell therapy in older recipients

The Journal of Thoracic and Cardiovascular Surgery
Yufeng ZhuoRen-Ke Li

Abstract

Cell therapy has received much attention for its potential to regenerate ischemic organs, but initial clinical trials in aged patients did not replicate the dramatic benefits recorded in preclinical studies with young animals. This study was designed to improve our understanding of age-related changes in the response to ischemic injury and the regenerative capacity of implanted cells in the context of cell therapy for older recipients. Restoration of regional perfusion after hind limb femoral artery ligation was impaired (P < .05) in old (vs young) rats, reflecting approximately 50% reductions in circulating endothelial progenitor cells and the release of vascular endothelial growth factor/basic fibroblast growth factor. Bone marrow stromal cells from young or old donors implanted into the ischemic hind limbs of young or old rats restored regional perfusion. Specifically, we documented significantly greater (P < .05) angiogenic potential in young (vs old) donor cells when recipient age was controlled and greater (P < .05) regenerative responses in young (vs old) recipients when donor cell age was controlled. Contributing to these differences were significantly greater survival in young (vs old) donor cells (in vitro and after i...Continue Reading

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