title: Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells.
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. Stem Cells 2017;35:1303-1315.
authors.affiliation: Genetics Institute, Gainesville, Florida, USA.|College of Medicine, Gainesville, Florida, USA.|Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Salazar
authors.affiliation: Wells Center for Pediatric Research, Indianapolis, Indiana, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Richardson
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Beli
authors.affiliation: Department of Anesthesia, Indianapolis, Indiana, USA.|Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Ripsch
authors.affiliation: College of Medicine, Gainesville, Florida, USA.
authors.forename: John
authors.initials: J
authors.lastname: George
authors.affiliation: Department of Anesthesia, Indianapolis, Indiana, USA.
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Leni
authors.initials: L
authors.lastname: Moldovan
authors.affiliation: Genetics Institute, Gainesville, Florida, USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Ashay
authors.initials: A
authors.lastname: Bhatwadekar
authors.affiliation: Department of Anesthesia, Indianapolis, Indiana, USA.
authors.forename: Vaishnavi
authors.initials: V
authors.lastname: Jadhav
authors.affiliation: Department of Anesthesia, Indianapolis, Indiana, USA.
authors.forename: Jared A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Department of Biostatistics, Gainesville, Florida, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: McGorray
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Bertone
authors.affiliation: Krannert Institute of Cardiology, Indianapolis, Indiana, USA.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana, USA.
authors.forename: Dmitri O
authors.initials: DO
authors.lastname: Traktuev
authors.affiliation: Krannert Institute of Cardiology, Indianapolis, Indiana, USA.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, Gainesville, Florida, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Colon-Perez
authors.affiliation: Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indianapolis, Indiana, USA.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Avin
authors.affiliation: Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Sims
authors.affiliation: Wells Center for Pediatric Research, Indianapolis, Indiana, USA.|Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mund
authors.affiliation: Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.|Scripps Clinic Medical Group, Scripps Center for Organ and Cell Transplantation, La Jolla, California, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Case
authors.affiliation: Mainland Acupuncture Center, Gainesville, Florida, USA.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Chon Buk National University, Jeonju, South Korea.
authors.forename: Min Su
authors.initials: MS
authors.lastname: Kim
authors.affiliation: McDavitt Veterinary Clinic, Zionsville, Indiana, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: McDavitt
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Boulton
authors.affiliation: Department of Pharmacology and Therapeutics, Gainesville, Florida, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Thinschmidt
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Li Calzi
authors.affiliation: Department of Psychiatry, Indianapolis, Indiana, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Fitz
authors.affiliation: Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indianapolis, Indiana, USA.
authors.forename: Robyn K
authors.initials: RK
authors.lastname: Fuchs
authors.affiliation: Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indianapolis, Indiana, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Warden
authors.affiliation: Department of Orthopedic Surgery, Indianapolis, Indiana, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: McKinley
authors.affiliation: Department of Psychiatry, Indianapolis, Indiana, USA.
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, Gainesville, Florida, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Johnson
authors.affiliation: Department of Molecular Genetics and Microbiology, Gainesville, Florida, USA.|School of Medicine, University of Electronic Science and Technology of China, Sichuan, China.
authors.forename: Lung-Ji
authors.initials: LJ
authors.lastname: Chang
authors.affiliation: The Brown Foundation, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Gao
authors.affiliation: The Brown Foundation, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Kolonin
authors.affiliation: Department of Radiation Oncology, College of Medicine, Gainesville, Florida, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Lai
authors.affiliation: Department of Radiation Oncology, College of Medicine, Gainesville, Florida, USA.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neuroscience, Center of Sensory Biology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Anesthesia, Indianapolis, Indiana, USA.|Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA.
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: White
authors.affiliation: College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Huisheng
authors.initials: H
authors.lastname: Xie
authors.affiliation: Wells Center for Pediatric Research, Indianapolis, Indiana, USA.|Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
authors.affiliation: Department of Ophthalmology, Indianapolis, Indiana, USA.
authors.forename: Maria B
authors.identifier: 0000-0002-3602-8844
authors.initials: MB
authors.lastname: Grant
mesh_terms: D000125:Achilles Tendon / Q000473:pathology; D015669:Acupuncture Points; D017667:Adipocytes / Q000166:cytology; D002001:Adipose Tissue, Brown / Q000166:cytology; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology*; D015671:Electroacupuncture; D005552:Forelimb / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D006801:Humans; D006930:Hyperalgesia / Q000628:therapy; D007031:Hypothalamus / Q000166:cytology; D016753:Interleukin-10 / Q000097:blood; D008264:Macrophages / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009415:Nerve Net / Q000502:physiology; D051381:Rats; D012421:Rupture; D011984:Sensory Receptor Cells / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000071256:Uncoupling Protein 1; D016753:Interleukin-10
keywords: Adult stem cells; Mesenchymal stem cells; Nervous system; Neurones