Electroacupuncture Promotes CNS-Dependent Release of Mesenchymal Stem Cells.

Author: Salazar TE1,2,3, Richardson MR4, Beli E2, Ripsch MS5, George J3, Kim Y5, Duan Y2, Moldovan L2, Yan Y1, Bhatwadekar A2, Jadhav V2, Smith JA5, McGorray S6, Bertone AL7, Traktuev DO8,9, March KL8,9, Colon-Perez LM10, Avin K11, Sims E12, Mund JA4,12, Case J4,12,13,14, Deng S15, Kim MS16, McDavitt B17, Boulton ME2, Thinschmidt J18, Li Calzi S2, Fitz SD11, Fuchs RK11, Warden SJ11, McKinley T19, Shekhar A20, Febo M10, Johnson PL21, Chang LJ22, Gao Z23, Kolonin MG23, Lai S24, Ma J24, Dong X25, White FA5, Xie H26, Yoder MC4,12, Grant MB2
Affiliation: <sup>1</sup>Genetics Institute, University of Florida, Gainesville, FL, 32610, USA. <sup>2</sup>Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. <sup>3</sup>College of Medicine, University of Florida, Gainesville, FL, 32610, USA. <sup>4</sup>Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. <sup>5</sup>Department of Anesthesia, Indiana University, Indianapolis, IN, 46202, USA. <sup>6</sup>Department of Biostatistics, University of Florida, Gainesville, FL, 32610, USA. <sup>7</sup>Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, 43210, USA. <sup>8</sup>Krannert Institute of Cardiology, Indiana University, Indianapolis, IN, 46202, USA. <sup>9</sup>Indiana Center for Vascular Biology and Medicine, Indiana University, Indianapolis, IN, 46202, USA. <sup>10</sup>Department of Psychiatry, University of Florida, McKnight Brain Institute, Gainesville, FL, 32610, USA. <sup>11</sup>Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indianapolis, IN, 46202, USA. <sup>12</sup>Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, 46202, USA. <sup>13</sup>Scripps Clinic Medical Group, Scripps Center for Organ and Cell Transplantation, La Jolla, CA, 92037, USA. <sup>14</sup>Department of Pediatrics, Indiana University, Indianapolis, IN, 46202, USA. <sup>15</sup>Mainland Acupuncture, Gainesville, FL, 32653, USA. <sup>16</sup>College of Veterinary Medicine, Chon Buk National University, Jeonju, South Korea. <sup>17</sup>McDavitt Veterinary Clinic, Zionsville, IN, 46077, USA. <sup>18</sup>Department of Pharmacology, University of Florida, Gainesville, FL, 32610, USA. <sup>19</sup>Department of Orthopedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. <sup>20</sup>Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. <sup>21</sup>Department of Anatomy &amp; Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. <sup>22</sup>Department of Molecular Genetics &amp; Microbiology, University of Florida, Gainesville, FL, 32611, USA. <sup>23</sup>Center for Metabolic and Degenerative Diseases, Harry E. Bovay Institute of Molecular Medicine University of Texas Health Science Center, Houston, TX, 77030, USA. <sup>24</sup>Department of Radiation Oncology, University of Florida School of Medicine, Gainesville, FL, 32610, USA. <sup>25</sup>Department of Neuroscience, Center of Sensory Biology, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. <sup>26</sup>College of Veterinary Medicine, University of Florida, Gainesville, FL, 32608, USA.
Conference/Journal: Stem Cells.
Date published: 2017 Mar 16
Other: Special Notes: doi: 10.1002/stem.2613. [Epub ahead of print] , Word Count: 225


Electro-acupuncture (EA) performed in rats and humans using front-limb acupuncture sites, LI-4 and LI-11, and Du-14 and Du-20 increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSC) 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 IL-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 directed at hind limb immune points, ST-36 and Liv-3 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. This article is protected by copyright. All rights reserved.

© 2017 AlphaMed Press.

KEYWORDS: Adult stem cells; Mesenchymal stem cells; Nervous system; Neurones

PMID: 28299842 DOI: 10.1002/stem.2613