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Research Paper|Volume 15, Issue 17|pp 9167—9181

Human adipose-derived stem cells preconditioned with a novel herbal formulation Jing Shi attenuate doxorubicin-induced cardiac damage

Dennis Jine-Yuan Hsieh1,2, Bruce Chi-Kang Tsai3, Parthasarathi Barik3, Marthandam Asokan Shibu4, Chia-Hua Kuo5,6, Wei-Wen Kuo7,8, Pi-Yu Lin9, Cheng-Yen Shih10, Shinn-Zong Lin11,12, Tsung-Jung Ho12,13,14, Chih-Yang Huang3,15,16,17,18
  • 1School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
  • 2Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 3Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
  • 4Department of Biotechnology, Bharathiar University, Coimbatore, India
  • 5Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
  • 6Department of Kinesiology and Health Science, College of William and Mary, Williamsburg, USA
  • 7Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
  • 8Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan
  • 9Buddhist Compassion Relief Tzu Chi Foundation, Hualien, Taiwan
  • 10Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
  • 11Department of Neurosurgery, Hualien Tzu Chi Hospital, Hualien, Taiwan
  • 12Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
  • 13Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
  • 14School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan
  • 15Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
  • 16Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan
  • 17Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan
  • 18Graduate Institute of Basic Medical Science, China Medical University, Taichung City, Taiwan
* Equal contribution
Received: May 15, 2023Accepted: August 21, 2023
https://doi.org/10.18632/aging.205026

Copyright: © 2023 Hsieh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pathological cardiac hypertrophy is a considerable contributor to global disease burden. Chinese herbal medicine (CHM) has been used to treat cardiovascular diseases since antiquity. Enhancing stem cell-mediated recovery through CHM represents a promising approach for protection against doxorubicin (Dox)-induced cardiac hypertrophy. Herein, we investigated whether human adipose-derived stem cells (hADSCs) preconditioned with novel herbal formulation Jing Si (JS) improved protective ability of stem cells against doxorubicin-induced cardiac damage. The effect of JS on hADSC viability and migration capacity was determined via MTT and migration assays, respectively. Co-culture of hADSC or JS-preconditioned hADSCs with H9c2 cells was analyzed with immunoblot, flow cytometry, TUNEL staining, LC3B staining, F-actin staining, and MitoSOX staining. The in vivo study was performed M-mode echocardiography after the treatment of JS and JS-preconditioned hADSCs by using Sprague Dawley (SD) rats. Our results indicated that JS at doses below 100 μg/mL had less cytotoxicity in hADSC and JS-preconditioned hADSCs exhibited better migration. Our results also revealed that DOX enhanced apoptosis, cardiac hypertrophy, and mitochondrial reactive oxygen species in DOX-challenged H9c2 cells, while H9c2 cells co-cultured with JS-preconditioned hADSCs alleviated these effects. It also enhanced the expression of autophagy marker LC3B, mTOR and CHIP in DOX-challenged H9c2 cells after co-culture with JS-preconditioned hADSCs. In Dox-challenged rats, the ejection fraction and fractional shortening improved in DOX-challenged SD rats exposed to JS-preconditioned hADSCs. Taken together, our data indicate that JS-preconditioned stem cells exhibit a cardioprotective capacity both in vitro and in vivo, highlighting the value of this therapeutic approach for regenerative therapy.