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

Tatiana E. Salazar; Matthew R. Richardson; Eleni Beli; Matthew S. Ripsch; John George; Youngsook Kim; Yaqian Duan; Leni Moldovan; Yuanqing Yan; Ashay Bhatwadekar; Vaishnavi Jadhav; Jared A. Smith; Susan McGorray; Alicia L. Bertone; Dmitri O. Traktuev; Keith L. March; Luis M. Colon-Perez; Keith G. Avin; Emily Sims; Julie A. Mund; Jamie Case; Xiaolin Deng; Min Su Kim; Bruce McDavitt; Michael E. Boulton; Jeffrey Thinschmidt; Sergio Li Calzi; Stephanie D. Fitz; Robyn K. Fuchs; Stuart J. Warden; Todd McKinley; Anantha Shekhar; Marcelo Febo; Phillip L. Johnson; Lung Ji Chang; Zhanguo Gao; Mikhail G. Kolonin; Song Lai; Jingfeng Ma; Xinzhong Dong; Fletcher A. White; Huisheng Xie; Mervin C. Yoder; Maria B. Grant

doi:10.1002/stem.2613

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

Tatiana E. Salazar, Matthew R. Richardson, Eleni Beli, Matthew S. Ripsch, John George, Youngsook Kim, Yaqian Duan, Leni Moldovan, Yuanqing Yan, Ashay Bhatwadekar, Vaishnavi Jadhav, Jared A. Smith, Susan McGorray, Alicia L. Bertone, Dmitri O. Traktuev, Keith L. March, Luis M. Colon-Perez, Keith G. Avin, Emily Sims, Julie A. MundJamie Case, Xiaolin Deng, Min Su Kim, Bruce McDavitt, Michael E. Boulton, Jeffrey Thinschmidt, Sergio Li Calzi, Stephanie D. Fitz, Robyn K. Fuchs, Stuart J. Warden, Todd McKinley, Anantha Shekhar, Marcelo Febo, Phillip L. Johnson, Lung Ji Chang, Zhanguo Gao, Mikhail G. Kolonin, Song Lai, Jingfeng Ma, Xinzhong Dong, Fletcher A. White, Huisheng Xie, Mervin C. Yoder^*, Maria B. Grant

^*Corresponding author for this work

Surgery, Thoracic Surgery Division

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1303-1315
Number of pages	13
Journal	Stem Cells
Volume	35
Issue number	5
DOIs	https://doi.org/10.1002/stem.2613
State	Published - May 2017

Funding

We thank the Angio BioCore at Indiana University School of Medicine for their work in the human studies, the Flow Cytometry Resource Facility at Indiana University Simon Cancer Center (partially funded by National Cancer Institute Grant P30. CA082709), the OSUCCC Microarray Shared Resource, where the equine GeneChips were processed, and Christopher Brown for his original illustration, the graphical abstract. This work was supported by NIH Grants R01EY012601-15, R01HL11070-03, R01DK090730-04, and R01EY007739-23 (to M.B.G.), U54 DK106846-01 and R01 HL109602 (to M.C.Y.), PR151924 (to M.E.B.), and DK100905, R01DK100905 and 101BX002209 (to F.A.W.), by the St. Vincent Foundation (to F.A.W.) and by the Cryptic Masons’ Medical Research Foundation (to K.L.M. and D.T.).

Keywords

Adult stem cells
Mesenchymal stem cells
Nervous system
Neurones

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/stem.2613

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Salazar, T. E., Richardson, M. R., Beli, E., Ripsch, M. S., George, J., Kim, Y., Duan, Y., Moldovan, L., Yan, Y., Bhatwadekar, A., Jadhav, V., Smith, J. A., McGorray, S., Bertone, A. L., Traktuev, D. O., March, K. L., Colon-Perez, L. M., Avin, K. G., Sims, E., ... Grant, M. B. (2017). Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells. Stem Cells, 35(5), 1303-1315. https://doi.org/10.1002/stem.2613

@article{354268f22d4f4f6181160ae768c2f277,

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.",

keywords = "Adult stem cells, Mesenchymal stem cells, Nervous system, Neurones",

author = "Salazar, \{Tatiana E.\} and Richardson, \{Matthew R.\} and Eleni Beli and Ripsch, \{Matthew S.\} and John George and Youngsook Kim and Yaqian Duan and Leni Moldovan and Yuanqing Yan and Ashay Bhatwadekar and Vaishnavi Jadhav and Smith, \{Jared A.\} and Susan McGorray and Bertone, \{Alicia L.\} and Traktuev, \{Dmitri O.\} and March, \{Keith L.\} and Colon-Perez, \{Luis M.\} and Avin, \{Keith G.\} and Emily Sims and Mund, \{Julie A.\} and Jamie Case and Xiaolin Deng and Kim, \{Min Su\} and Bruce McDavitt and Boulton, \{Michael E.\} and Jeffrey Thinschmidt and \{Li Calzi\}, Sergio and Fitz, \{Stephanie D.\} and Fuchs, \{Robyn K.\} and Warden, \{Stuart J.\} and Todd McKinley and Anantha Shekhar and Marcelo Febo and Johnson, \{Phillip L.\} and Chang, \{Lung Ji\} and Zhanguo Gao and Kolonin, \{Mikhail G.\} and Song Lai and Jingfeng Ma and Xinzhong Dong and White, \{Fletcher A.\} and Huisheng Xie and Yoder, \{Mervin C.\} and Grant, \{Maria B.\}",

note = "Publisher Copyright: {\textcopyright} 2017 AlphaMed Press",

year = "2017",

month = may,

doi = "10.1002/stem.2613",

language = "English (US)",

volume = "35",

pages = "1303--1315",

journal = "Stem Cells",

issn = "1066-5099",

publisher = "Oxford University Press",

number = "5",

}

Salazar, TE, Richardson, MR, Beli, E, Ripsch, MS, George, J, Kim, Y, Duan, Y, Moldovan, L, Yan, Y, Bhatwadekar, A, Jadhav, V, Smith, JA, McGorray, S, Bertone, AL, Traktuev, DO, March, KL, Colon-Perez, LM, Avin, KG, Sims, E, Mund, JA, Case, J, Deng, X, Kim, MS, McDavitt, B, Boulton, ME, Thinschmidt, J, Li Calzi, S, Fitz, SD, Fuchs, RK, Warden, SJ, McKinley, T, Shekhar, A, Febo, M, Johnson, PL, Chang, LJ, Gao, Z, Kolonin, MG, Lai, S, Ma, J, Dong, X, White, FA, Xie, H, Yoder, MC & Grant, MB 2017, 'Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells', Stem Cells, vol. 35, no. 5, pp. 1303-1315. https://doi.org/10.1002/stem.2613

TY - JOUR

T1 - Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells

AU - Salazar, Tatiana E.

AU - Richardson, Matthew R.

AU - Beli, Eleni

AU - Ripsch, Matthew S.

AU - George, John

AU - Kim, Youngsook

AU - Duan, Yaqian

AU - Moldovan, Leni

AU - Yan, Yuanqing

AU - Bhatwadekar, Ashay

AU - Jadhav, Vaishnavi

AU - Smith, Jared A.

AU - McGorray, Susan

AU - Bertone, Alicia L.

AU - Traktuev, Dmitri O.

AU - March, Keith L.

AU - Colon-Perez, Luis M.

AU - Avin, Keith G.

AU - Sims, Emily

AU - Mund, Julie A.

AU - Case, Jamie

AU - Deng, Xiaolin

AU - Kim, Min Su

AU - McDavitt, Bruce

AU - Boulton, Michael E.

AU - Thinschmidt, Jeffrey

AU - Li Calzi, Sergio

AU - Fitz, Stephanie D.

AU - Fuchs, Robyn K.

AU - Warden, Stuart J.

AU - McKinley, Todd

AU - Shekhar, Anantha

AU - Febo, Marcelo

AU - Johnson, Phillip L.

AU - Chang, Lung Ji

AU - Gao, Zhanguo

AU - Kolonin, Mikhail G.

AU - Lai, Song

AU - Ma, Jingfeng

AU - Dong, Xinzhong

AU - White, Fletcher A.

AU - Xie, Huisheng

AU - Yoder, Mervin C.

AU - Grant, Maria B.

PY - 2017/5

Y1 - 2017/5

N2 - 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.

AB - 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.

KW - Adult stem cells

KW - Mesenchymal stem cells

KW - Nervous system

KW - Neurones

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UR - http://www.scopus.com/inward/citedby.url?scp=85018836293&partnerID=8YFLogxK

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DO - 10.1002/stem.2613

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AN - SCOPUS:85018836293

SN - 1066-5099

VL - 35

SP - 1303

EP - 1315

JO - Stem Cells

JF - Stem Cells

IS - 5

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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