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Changes in the Thickness of Rat Nerve Sheaths after Single Subperineural Administration of Rat Bone Marrow Mesenchymal Stem Cells

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Bulletin of Experimental Biology and Medicine Aims and scope

The sheaths of the damaged peripheral nerve of Wistar-Kyoto rats were studied after single subperineural administration of bromodeoxyuridine (BrdU)-labeled bone marrow mesenchymal stem cells (MSC) from the same rats. The sciatic nerve was damaged by ligation for 40 sec directly before MSC administration. BrdU+ MSC were identified in the recipient nerve within 1 week after transplantation and were detected not only in the endoneurium, but also in the epineurium and perineurium. It was found that single administration of MSC into the damaged nerve trunk led to an almost 2-fold increase in the thickness of its sheaths (perineurium and epineurium) in comparison with the control group (ligation). It can be hypothesized that MSC induce thickening of nerve sheaths through the production of factors that stimulate angiogenesis and adipogenesis.

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References

  1. Arutyunyan IV, Fatkhudinov TKh, Elchaninov AV, Makarov AV, Vasyukova OA, Usman NY, Marey MV, Volodina MA, Kananykhina EY, Lokhonina AV, Bolshakova GB, Goldshtein DV, Sukhikh GT. Understanding mechanisms of the umbilical cord-derived multipotent mesenchymal stromal cell-mediated recovery enhancement in rat model of limb ischemia. Geny Kletki. 2018;13(1):82-89. doi: https://doi.org/10.23868/201805010. Russian.

    Article  Google Scholar 

  2. Zin’kova NN, Sokolova IB, Viide SK, Shvedova EV, Alexandrov GV, Kruglyakov PV, Polyntsev DG, Gilerovich EG. Mesenchymal stem cell therapy of brain ischemic stroke in rats. Cell Tissue Biol. 2007;1(5):389-398.

    Article  Google Scholar 

  3. Karagyaur MN, Makarevich PI, Shevchenko EK, Stambolsky DV, Kalinina NI, Parfyonova YeV. Modern approaches to peripheral nerve regeneration after injury: the prospects of gene and cell therapy. Geny Kletki. 2017;12(1):6-14. doi: https://doi.org/10.23868/201703001. Russian.

  4. Masgutov RF, Masgutova GA, Mukhametova LR, Idrisova KF, Mullakhmetova AF, Syromiatnikova VY, Bogov AA, Salafutdinov II, Arkhipova SS, Salikhov RZ, Rizvanov AA. Results of a comparative valuation of the efficiency of using the plasmid construct pBud-VEGF165-FGF2 in models of autograft of the sciatic nerve defect and tubulation with the Neuragen® collagen tube. Geny Kletki. 2020;15(4):61-65. doi: https://doi.org/10.23868/202012010. Russian.

  5. Shchanitsyn IN, Ivanov AN, Bazhanov SP, Ninel’ VG, Puchin’jan DM, Norkin IA. Stimulation of peripheral nerve regeneration: current status, problems and perspectives. Uspekhi Fiziol. Nauk. 2017;48(3):92-112. Russian.

  6. Boldyreva MА, Bondar IV, Stafeev IS, Makarevich PI, Beloglazova IB, Zubkova ES, Shevchenko EK, Molokotina YD, Karagyaur MN, Rаtner ЕI, Parfyonova YV. Plasmid-based gene therapy with hepatocyte growth factor stimulates peripheral nerve regeneration after traumatic injury. Biomed. Pharmacother. 2018;101:682-690. doi: https://doi.org/10.1016/j.biopha.2018.02.138

    Article  CAS  Google Scholar 

  7. Brett E, Chung N, Leavitt WT, Momeni A, Longaker MT, Wan DC. A review of cell-based strategies for soft tissue reconstruction. Tissue Eng. Part B. Rev. 2017;23(4):336-346. doi: https://doi.org/10.1089/ten.TEB.2016.0455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dong R, Liu Y, Yang Y, Wang H, Xu Y, Zhang Z. MSC-derived exosomes-based therapy for peripheral nerve injury: a novel therapeutic strategy. Biomed. Res. Int. 2019;2019:6458237. doi: https://doi.org/10.1155/2019/6458237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fatkhudinov TKh, Bol’shakova GB, Goldshtein DV, Sukhikh GT. Mechanisms of therapeutic activity of multipotent cells in heart diseases Mechanisms of therapeutic activity of multipotent cells in heart diseases. Bull. Exp. Biol. Med. 2014;156(4):535-543. doi: https://doi.org/10.1007/s10517-014-2392-5

    Article  CAS  PubMed  Google Scholar 

  10. Grigorev IP, Korzhevskii DE. Current technologies for fixation of biological material for immunohistochemical analysis (review). Modern Technol. Med. 2018;10(2):156-165. doi: https://doi.org/10.17691/stm2018.10.2.19

    Article  Google Scholar 

  11. Kachgal S, Putnam AJ. Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms. Angiogenesis. 2011;14(1):47-59. doi: https://doi.org/10.1007/s10456-010-9194-9

    Article  CAS  PubMed  Google Scholar 

  12. Kalinina N, Klink G, Glukhanyuk E, Lopatina T, Efimenko A, Akopyan Z, Tkachuk V. miR-92a regulates angiogenic activity of adipose-derived mesenchymal stromal cells. Exp. Cell Res. 2015;339(1):61-66. doi: https://doi.org/10.1016/j.yexcr.2015.10.007

    Article  CAS  PubMed  Google Scholar 

  13. Kalinina NI, Sysoeva VY, Rubina KA, Parfenova YV, Tkachuk VA. Mesenchymal stem cells in tissue growth and repair. Acta Naturae. 2011;3(4):30-37.

    Article  CAS  Google Scholar 

  14. Kimura Y, Ozeki M, Inamoto T, Tabata Y. Time course of de novo adipogenesis in matrigel by gelatin microspheres incorporating basic fibroblast growth factor. Tissue Eng. 2002;8(4):603-613. doi: https://doi.org/10.1089/107632702760240526

    Article  CAS  PubMed  Google Scholar 

  15. Kucenas S. Perineurial glia. Cold Spring Harb. Perspect. Biol. 2015;7(6):a020511. doi: https://doi.org/10.1101/cshperspect.a020511

  16. Masgutov R, Masgutova G, Mullakhmetova A, Zhuravleva M, Shulman A, Rogozhin A, Syromiatnikova V, Andreeva D, Zeinalova A, Idrisova K, Allegrucci C, Kiyasov A, Rizvanov A. Adipose-derived mesenchymal stem cells applied in fibrin glue stimulate peripheral nerve regeneration. Front. Med. (Lausanne). 2019;6:68. doi: https://doi.org/10.3389/fmed.2019.00068

    Article  Google Scholar 

  17. Mathot F, Shin AY, Van Wijnen AJ. Targeted stimulation of MSC in peripheral nerve repair. Gene. 2019;710:17-23. doi: https://doi.org/10.1016/j.gene.2019.02.078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Murray LMA, Krasnodembskaya AD. Concise review: intercellular communication via organelle transfer in the biology and therapeutic applications of stem cells. Stem Cells. 2019;37(1):14-25. doi: https://doi.org/10.1002/stem.2922

    Article  PubMed  Google Scholar 

  19. Petrova ES. Injured nerve regeneration using cell-based therapies: current challenges. Acta Naturae. 2015;7(3):38-47.

    Article  CAS  Google Scholar 

  20. Petrova ES, Isaeva EN. Effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve. Izv. Akad. Nauk Ser. Biol. 2014;(6):549-556.

    Google Scholar 

  21. Petrova E, Isaeva E, Kolos E, Korzhevskii D. Allogeneic bone marrow mesenchymal stem cells in the epineurium and perineurium of the recipient rat. Biol. Communications. 2018;63(2):123-132. doi: https://doi.org/10.21638/spbu03.2018.205

    Article  Google Scholar 

  22. Scavo LM, Karas M, Murray M, Leroith D. Insulin-like growth factor-I stimulates both cell growth and lipogenesis during differentiation of human mesenchymal stem cells into adipocytes. J. Clin. Endocrinol. Metab. 2004;89(7):3543-3553. doi: https://doi.org/10.1210/jc.2003-031682

    Article  CAS  PubMed  Google Scholar 

  23. Server A, Reina MA, Boezaart AP, Prats-Galino A, Esteves Coelho M, Sala-Blanch X. Microanatomical nerve architecture of 6 mammalian species: is trans-species translational anatomic extrapolation valid? Reg. Anesth. Pain Med. 2018;43(5):496-501. doi: https://doi.org/10.1097/AAP.0000000000000772

    Article  PubMed  Google Scholar 

  24. Sukhinich KK, Dashinimaev EB, Vorotelyak EA, Aleksandrova MA. Regenerative effects of solid neural tissue grafts located in gelatin hydrogel conduit for treatment of peripheral nerve injury. Plast. Reconstr. Surg. Glob. Open. 2020;8(2):e2610. doi: https://doi.org/10.1097/GOX.0000000000002610

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sukhinich KK, Namestnikova DD, Gubskii IL, Gabashvili AN, Mel’nikov PA, Vitushev EY, Vishnevskii DA, Revkova VA, Solov’eva AA, Voitkovskaya KS, Vakhrushev IV, Burunova VV, Berdalin AB, Aleksandrova MA, Chekhonin VP, Gubskii LV, Yarygin KN. Distribution and migration of human placental mesenchymal stromal cells in the brain of healthy rats after stereotaxic or intra-arterial transplantation. Bull. Exp. Biol. Med. 2020;168(4):542-551. doi: https://doi.org/10.1007/s10517-020-04750-8

    Article  CAS  PubMed  Google Scholar 

  26. Tabata Y, Miyao M, Inamoto T, Ishii T, Hirano Y, Yamaoki Y, Ikada Y. De novo formation of adipose tissue by controlled release of basic fibroblast growth factor. Tissue Eng. 2000;6(3):279-289. doi: https://doi.org/10.1089/10763270050044452

    Article  CAS  PubMed  Google Scholar 

  27. Topp KS, Boyd BS. Peripheral nerve: from the microscopic functional unit of the axon to the biomechanically loaded macroscopic structure. J. Hand Ther. 2012;25(2):142-151; quiz 152. doi: https://doi.org/10.1016/j.jht.2011.09.002

    Article  PubMed  Google Scholar 

  28. Toriyama K, Kawaguchi N, Kitoh J, Tajima R, Inou K, Kitagawa Y, Torii S. Endogenous adipocyte precursor cells for regenerative soft-tissue engineering. Tissue Eng. 2002;8(1):157-165. doi: https://doi.org/10.1089/107632702753503144

    Article  CAS  PubMed  Google Scholar 

  29. Weiss DJ, English K, Krasnodembskaya A, Isaza-Correa JM, Hawthorne IJ, Mahon BP. The necrobiology of mesenchymal stromal cells affects therapeutic efficacy. Front. Immunol. 2019;10:1228. doi: https://doi.org/10.3389/fimmu.2019.01228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wu P, Zhang B, Shi H, Qian H, Xu W. MSC-exosome: A novel cell-free therapy for cutaneous regeneration. Cytotherapy. 2018;20(3):291-301. doi: https://doi.org/10.1016/j.jcyt.2017.11.002

    Article  PubMed  Google Scholar 

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Correspondence to E. S. Petrova.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 123-129, June, 2021

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Petrova, E.S., Kolos, E.A. & Korzhevskii, D.E. Changes in the Thickness of Rat Nerve Sheaths after Single Subperineural Administration of Rat Bone Marrow Mesenchymal Stem Cells. Bull Exp Biol Med 171, 547–552 (2021). https://doi.org/10.1007/s10517-021-05267-4

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  • DOI: https://doi.org/10.1007/s10517-021-05267-4

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