Author + information
- Received March 11, 2017
- Revision received May 2, 2017
- Accepted July 20, 2017
- Published online December 25, 2017.
- Hui-Fang Song, MD, PhDa,b,c,
- Sheng He, MD, PhDb,c,d,
- Shu-Hong Li, MD, MScc,
- Wen-Juan Yin, MD, MScb,
- Jun Wu, MD, MScc,
- Jian Guo, MD, PhDc,
- Zheng-Bo Shao, MD, PhDc,e,
- Xiao-Yan Zhai, MD, PhDb,
- Hui Gong, MD, PhDb,
- Li Lu, MD, PhDa,
- Fang Wei, MD, PhDd,
- Richard D. Weisel, MDc,f,
- Jun Xie, MD, PhDb,∗ ( and )
- Ren-Ke Li, MD, PhDc,f,∗∗ ()
- aDepartment of Anatomy, Shanxi Medical University, Taiyuan, China
- bShanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China
- cDivision of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Canada
- dFirst Hospital of Shanxi Medical University, Taiyuan, China
- eDepartment of Ophthalmology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
- fDivision of Cardiac Surgery, Department of Surgery, University of Toronto, Toronto, Canada
- ↵∗Addresses for correspondence:
Dr. Jun Xie, Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.
- ↵∗∗Dr. Ren-Ke Li, Division of Cardiac Surgery, Department of Surgery, University of Toronto, Toronto Medical Discovery Tower, Room 3-702, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
• 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.
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.
This work was supported by the 331 Early Career Researcher Grant from the Basic Medical School, Shanxi Medical University (no. 201217) awarded to Dr. Xie; and a Foundation grant from the Canadian Institutes of Health Research (no. 332652) award to Dr. Li. Dr. Li holds a Tier 1 Canada Research Chair in Cardiac Regeneration. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 11, 2017.
- Revision received May 2, 2017.
- Accepted July 20, 2017.
- 2017 The Authors