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JACC Basic Transl Sci. 2017 Nov 29;2(6):702-716. doi: 10.1016/j.jacbts.2017.07.014. eCollection 2017 Dec.

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

Song HF1,2,3, He S2,3,4, Li SH3, Yin WJ2, Wu J3, Guo J3, Shao ZB3,5, Zhai XY2, Gong H2, Lu L1, Wei F4, Weisel RD3,6, Xie J2, Li RK3,6.

Author information

1
Department of Anatomy, Shanxi Medical University, Taiyuan, China.
2
Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China.
3
Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Canada.
4
First Hospital of Shanxi Medical University, Taiyuan, China.
5
Department of Ophthalmology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
6
Division of Cardiac Surgery, Department of Surgery, University of Toronto, Toronto, Canada.

Abstract

Reduced regenerative capacity of aged stem cells hampers the benefits of autologous cell therapy for cardiac regeneration. This study investigated whether neuron-derived neurotrophic factor (NDNF) could rejuvenate aged human bone marrow (hBM)- multipotent mesenchymal stromal cells (MSCs) and whether the rejuvenated hBM-MSCs could improve cardiac repair after ischemic injury. Over-expression of NDNF in old hBM-MSCs decreased cell senescence and apoptosis. Engraftment of NDNF over-expressing old hBM-MSCs into the ischemic area of mouse hearts resulted in improved cardiac function after myocardial infarction, while promoting implanted stem cell survival. Our findings suggest NDNF could be a new factor to rejuvenate aged stem cells and improve their capability to repair the aged heart after injury.

KEYWORDS:

CDC, cardiosphere-derived cell; MI, myocardial infarction; MSC, multipotent mesenchymal stromal cell; NDNF; NDNF, neuron-derived neurotrophic factor; RGN, regucalcin; aging; hBM, human bone marrow; heart function; human stem cells; mRNA, messenger ribonucleic acid; myocardial infarction; p-Akt, phosphorylated Akt; rejuvenation

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