Aged Human Multipotent Mesenchymal Stromal Cells Can Be Rejuvenated by Neuron-Derived Neurotrophic Factor and Improve Heart Function After Injury.

•The benefits of cell transplantation for cardiac repair are diminished in older individuals and effective methods to rejuvenate aged stem cells are needed to treat the increasing number of older patients with heart failure.•Over-expressing NDNF in old hBM-MSCs rejuvenated the cells, increasing their proliferative capacity and reducing cellular apoptosis.•In vivo engraftment of NDNF-overexpressing old hBM-MSCs into the ischemic area of mouse hearts improved cardiac function after myocardial infarction, while promoting engrafted stem cell survival and proliferation and decreasing cell senescence.•NDNF rejuvenated aged human stem cells, improving their capability to repair the aged heart after ischemic injury through Activation of Akt singling.