1. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan.
2. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
3. Department of Healthcare Administration, Asia University, Taichung, 413, Taiwan.
4. Department of Biological Science and Technology, China Medical University, 404, Taichung, Taiwan.
5. Department of Neurological Surgery,Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
6. Department of Psychiatry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan.
7. School of Medicine Tzu Chi University, Hualien 970, Taiwan.
8. Department of Sports Sciences, University of Taipei, Taipei, 111, Taiwan.
9. Department of Nursing, MeiHo University, Pingtung, 912, Taiwan.
10. Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam.
11. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei, 235, Taiwan.
12. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan.
13. Department of Biological Science and Technology, Asia University, Taichung 413, Taiwan.
14. Cardiovascular and Mitochondria related diseases research center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan.
15. Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan.
*These authors share equal contributions.
Aging is the most important current issue and is usually accompanied by complications, such as cardiovascular disorders and neurodegenerative diseases, which are the leading causes of death worldwide and the second major cause of death in Taiwan. In this study, we have investigated the protective effect of adipose-derived mesenchymal stem cells (ADSCs) and the role of epigallocatechin gallate (EGCG) in enhancing this effect in aging cerebral cortex of rats. Further, we attempted to elucidate the molecular mechanism through which EGCG influences the protective effects of ADSC. ADSCs, co-cultured with EGCG, were injected into 20-month-old Wistar rats. Hematoxylin and eosin staining of the cerebral cortex revealed noticeable neurogenic activity and visible improvements in the integrity of the pre-frontal cortex tissue, compared to that in rats treated with ADSCs alone. Western blot analysis confirmed that ADSC, co-cultured with EGCG, enhanced cell survival via the p-Akt pathway and improved mitochondrial biogenesis via the SIRT-1 pathway. Moreover, it increased the available brain-derived neurotrophic factor to a higher degree than that in the ADSC group. Furthermore, western blotting showed that EGCG improved the antioxidant activity of the ADSCs in the cortex tissues via the Nrf-2 and HO-1 pathway. Based on these findings, we propose that this variation in stem cell treatment may facilitate functional recovery and enhanced neuroprotection in aged brains.
Keywords: Adipose-derived mesenchymal stem cells, epigallocatechin gallate, aging, neuroprotection