Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells

Author:

Salazar Tatiana E.123,Richardson Matthew R.4,Beli Eleni2,Ripsch Matthew S.56,George John3,Kim Youngsook5,Duan Yaqian2,Moldovan Leni2,Yan Yuanqing1,Bhatwadekar Ashay2,Jadhav Vaishnavi5,Smith Jared A.5,McGorray Susan7,Bertone Alicia L.8,Traktuev Dmitri O.910,March Keith L.910,Colon-Perez Luis M.11,Avin Keith G.12,Sims Emily13,Mund Julie A.413,Case Jamie1314,Deng Xiaolin15,Kim Min Su16,McDavitt Bruce17,Boulton Michael E.2,Thinschmidt Jeffrey18,Li Calzi Sergio2,Fitz Stephanie D.19,Fuchs Robyn K.12,Warden Stuart J.12,McKinley Todd20,Shekhar Anantha19,Febo Marcelo11,Johnson Phillip L.21,Chang Lung-Ji2223,Gao Zhanguo24,Kolonin Mikhail G.24,Lai Song25,Ma Jingfeng25,Dong Xinzhong26,White Fletcher A.56,Xie Huisheng27,Yoder Mervin C.413,Grant Maria B.2ORCID

Affiliation:

1. a Genetics Institute, Gainesville, Florida, USA

2. b Department of Ophthalmology, Indianapolis, Indiana, USA

3. c College of Medicine, Gainesville, Florida, USA

4. d Wells Center for Pediatric Research, Indianapolis, Indiana, USA

5. e Department of Anesthesia, Indianapolis, Indiana, USA

6. f Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA

7. g Department of Biostatistics, Gainesville, Florida, USA

8. h Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, USA

9. i Krannert Institute of Cardiology, Indianapolis, Indiana, USA

10. j Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana, USA

11. k Department of Psychiatry, McKnight Brain Institute, Gainesville, Florida, USA

12. l Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indianapolis, Indiana, USA

13. m Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA

14. n Scripps Clinic Medical Group, Scripps Center for Organ and Cell Transplantation, La Jolla, California, USA

15. o Mainland Acupuncture Center, Gainesville, Florida, USA

16. ppCollege of Veterinary Medicine, Chon Buk National University, Jeonju, South Korea

17. q McDavitt Veterinary Clinic, Zionsville, Indiana, USA

18. r Department of Pharmacology and Therapeutics, Gainesville, Florida, USA

19. s Department of Psychiatry, Indianapolis, Indiana, USA

20. t Department of Orthopedic Surgery, Indianapolis, Indiana, USA

21. u Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA

22. v School of Medicine, University of Electronic Science and Technology of China, Sichuan, China

23. w Department of Molecular Genetics and Microbiology, Gainesville, Florida, USA

24. x The Brown Foundation, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA

25. y Department of Radiation Oncology, College of Medicine, Gainesville, Florida, USA

26. z Department of Neuroscience, Center of Sensory Biology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

27. aa College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA

Abstract

Abstract Electroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 and LI-11, and GV-14 and GV-20 (humans) and Bai-hui (rats) increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSCs) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue, whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation. EA-mediated SNS activation was further supported by browning of white adipose tissue in rats. EA treatment of rats undergoing partial rupture of the Achilles tendon resulted in reduced mechanical hyperalgesia, increased serum interleukin-10 levels and tendon remodeling, effects blocked in propranolol-treated rodents. To distinguish the afferent role of the peripheral nervous system, phosphoinositide-interacting regulator of transient receptor potential channels (Pirt)-GCaMP3 (genetically encoded calcium sensor) mice were treated with EA acupuncture points, ST-36 and LIV-3, and GV-14 and Bai-hui and resulted in a rapid activation of primary sensory neurons. EA activated sensory ganglia and SNS centers to mediate the release of MSC that can enhance tissue repair, increase anti-inflammatory cytokine production and provide pronounced analgesic relief.

Funder

NIH

Cryptic Masons’ Medical Research Foundation

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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