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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.

SUBMITTER: Salazar TE

PROVIDER: S-EPMC5530374 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Salazar Tatiana E TE Richardson Matthew R MR Beli Eleni E Ripsch Matthew S MS George John J Kim Youngsook Y Duan Yaqian Y Moldovan Leni L Yan Yuanqing Y Bhatwadekar Ashay A Jadhav Vaishnavi V Smith Jared A JA McGorray Susan S Bertone Alicia L AL Traktuev Dmitri O DO March Keith L KL Colon-Perez Luis M LM Avin Keith G KG Sims Emily E Mund Julie A JA Case Jamie J Deng Xiaolin X Kim Min Su MS McDavitt Bruce B Boulton Michael E ME Thinschmidt Jeffrey J Li Calzi Sergio S Fitz Stephanie D SD Fuchs Robyn K RK Warden Stuart J SJ McKinley Todd T Shekhar Anantha A Febo Marcelo M Johnson Phillip L PL Chang Lung-Ji LJ Gao Zhanguo Z Kolonin Mikhail G MG Lai Song S Ma Jingfeng J Dong Xinzhong X White Fletcher A FA Xie Huisheng H Yoder Mervin C MC Grant Maria B MB

Stem cells (Dayton, Ohio) 20170501 5

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 ...[more]

PMID: 28299842

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Project description:BackgroundDiabetes can cause extensive enteric nervous system (ENS) injuries and gastrointestinal motility disorder. In developing possible treatments, researchers have engaged in tissue regeneration engineering with the very promising bone marrow-derived mesenchymal stem cells (BMSCs). However, BMSCs have poor homing ability to the targeted tissues after intravenous injection. Thus, we aimed to investigate whether enhancing the expression of E-selectin ligand on BMSCs could improve their homing ability and subsequently influence their role in ENS remodeling in diabetic mice.MethodsFirst, we constructed the fucosylation modification of CD44 on BMSCs through a fucosyltransferase VII (FTVII) system to generate a Hematopoietic Cell E-/L-selectin Ligand (HCELL) property, a fucosylated sialyllactosaminyl glycovariant of CD44 that potently binds E-selectin. Next, FTVII-modified and unmodified BMSCs labeled with green fluorescent protein (GFP) were injected into diabetic mice through the tail vein to compare their homing ability to the gastrointestinal tract and their effect on ENS remodeling, respectively. A bioluminescent imaging system was used to evaluate the homing ability of GFP-labeled BMSCs with and without FTVII modification, to the gastrointestinal tract. Gastrointestinal motility was assessed by gastrointestinal transient time, defecation frequency, stool water content and colon strips contractility. Immunofluorescence staining and western blotting were used to assess the expression levels of protein gene product 9.5 (PGP9.5), glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor (GDNF).ResultsThe FTVII-mediated α(1,3)-fucosylation modification of CD44 on BMSCs generated a HCELL property. Bioluminescent imaging assays showed that FTVII-modified BMSCs had enhanced homing ability to gastrointestinal tract, mainly to the colon, 24 h after injection through the tail vein. Compared with diabetic mice, FTVII-modified BMSCs significantly promoted the gastrointestinal motility and the ENS remodeling, including intestinal peristalsis (P < 0.05), increased feces excretion (P < 0.05) and the water content of the feces (P < 0.05), restored the spontaneous contraction of the colon (P < 0.05), and upregulated the protein expression levels of PGP9.5 (P < 0.01), GFAP (P < 0.001), and GDNF (P < 0.05), while unmodified BMSCs did not (P > 0.05).ConclusionsCD44 fucosylation modification on murine BMSCs promotes homing ability to the gastrointestinal tract and ENS remodeling in diabetic mice.

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

Publications

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

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