Allogeneic bone marrow mesenchymal stem cells in the epineurium and perineurium of the recipient rat

  • Elena Petrova Laboratory of Functional Morphology of the Central and Peripheral Nervous System, Institute of Experimental Medicine, ul. Akad. Pavlova, 12, Saint Petersburg, 197376, Russian Federation
  • Elena Isaeva Laboratory of Immunoformacology, Research Institute of Highly Pure Biopreparations, Russian Federal Agency for Medicine and Biology, Pudozhskaya ul., 7, Saint Petersburg, 197110, Russian Federation
  • Elena Kolos Laboratory of Functional Morphology of the Central and Peripheral Nervous System, Institute of Experimental Medicine, ul. Akad. Pavlova, 12, Saint Petersburg, 197376, Russian Federation
  • Dmitrii Korzhevskii Laboratory of Functional Morphology of the Central and Peripheral Nervous System, Institute of Experimental Medicine, ul. Akad. Pavlova, 12, Saint Petersburg, 197376, Russian Federation


Achievements in regenerative medicine have demonstrated that using different kinds of stem cells can have some stimulating effect on the reparative regeneration processes of the nervous system. To stimulate nerve regeneration, the experimental elaboration of mesenchymal stem cell (MSC) transplantation is carried out actively. There is evidence that MSCs promote growth of the recipient regenerating axons after transplantation into the damaged nerve or the conduit. However, processes that happen in transplanted cells and these cells’ differentiation are poorly studied. The aim of the present study is to describe the localization and morphologically peculiar properties of bone marrow-derived mesenchymal stem cells after their allotransplantation into the injured nerve of a rat. MSCs from Wistar—Kyoto rats were cultivated for seven days and labeled with BrdU three days before using. The sciatic nerves of adult Wistar—Kyoto rats were damaged, and suspensions of BrdU-labeled cultured MSCs were immediately transplanted into the damaged sciatic nerves. Five to seven days after transplantation, the surviving MSCs were found. Using fluorescent microscopy, we found that some of the transplanted cells were localized in the epineurium and in the perineurium. Some of the transplanted MSCs differentiated into adipocytes and cells of the perineurium.


MSCs, differentiating, nerve, epineurium, perineurium, adipocytes, immunohistochemistry, fluorescence microscopy


Download data is not yet available.


Bogov, A. A., Masgutov, R. F., Rizvanov, A. A., Salafutdinov, I. I., Gallyamov, A. R., Hannanova, I. G., and Ahtyamov, I. F. 2016. Treatment of traumatic injuries of peripheral nerves with the use of regeneration stimulators. Annals of plastic, reconstructive and aesthetic surgery 1: 64–65.

Brohlin, M., Mahay, D., Novikov, L. N., Terenghi, G., Wiberg, M., Shawcross, S. G., and Novikova, L. N. 2009. Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells. Neuroscience Research 64:41–49.

Bunge, M. B., Wood, P. M., Tynan, L. B. Bates, M. L., and Sanes, J. R. 1989. Perineurium originates from fibroblasts: demonstration in vitro with a retroviral marker. Science 243(4888):229–231.

Chen, X., Wang, X. D., Chen, G. Lin, W. W., Yao, J., and Gu X. S. 2006. Study of in vivo differentiation of rat bone marrow stromal cells into schwann cell-like cells. Microsurgery 26(2): 111–115.

Chen, C. J., Ou, Y. C., Liao, S. L., Chen, W. Y., Wu, C. W., Wang, C. C., Wang, W. Y., Huang, Y. S., and Hsu, S. H. 2007. Transplantation of bone marrow stromal cells for peripheral nerve repair. Experimental Neurology 204: 443–445.

Chumasov, E. I. 1975. On the structure of perineurium of the peripheral nervous system. Arkhiv Anatomii, Gistologii i Embriologii 68(4):29–34.

Cohen, J. A., Imrey, P. B., Planchon, S. M., Bermel, R. A., Fisher, E., Fox, R. J., Bar-Or, A., Sharp, S. L., Skaramagas ,T. T., Jagodnik, P., Karafa, M., Morrison, S., Reese Koc, J., Gerson, S. L., and Lazarus, H. M. 2018. Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Multiple sclerosis 24(4):501–511.

Dennis, J. E. and Charbord, P. 2002. Origin and differentiation of human and murine stroma. Stem Cells 20(3):205–214.

Dezawa, M., Takahashi, I., Esaki, M., Takano, M., and Sawada, H. 2001. Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. European Journal of Neuroscience 14:1771–1776.

El’chaninov, A. V., Fatkhudinov, T. Kh., Arutyunyan, I. V., Makarov, A. V., Lokhonina, A. V. Eremina, I. Z., Bicherova, I. A., and Bol’shakova, G. B. 2017. Directions of allogeneic multipotent stromal cells differentiation in the regenerating liver. Journal of Anatomy and Histopathology 6(4):15-20.

Evaristo-Mendonca, F., Carrier-Ruiz, A., de Siqueira-Santos, R., Campos, R. M. P., Rangel, B., Kasai-Brunswick, T. H. and Ribeiro-Resende, V. T. 2018. Dual contribution of mesenchymal stem cells employed for tissue engineering of peripheral nerves: trophic activity and differentiation into connective-tissue cells. Stem Cell Reviews and Reports 14(2):200–212.

Fairbairn, N. G., Meppelink, A. M., Ng-Glazier, J., Randolph, M. A., and Winograd, J. M. 2015. Augmenting peripheral nerve regeneration using stem cells. World Journal of Stem Cells 7(1):11–26.

Frattini, F., Lopes, F. R., Almeida, F. M. Rodrigues, R. F., Boldrini, L. C., Tomaz, M. A., Baptista, A. F., Melo, P. A., and Martinez, A. M. 2012. Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury. Tissue Engeneering. Part. A. 18(19–20):2030–2039.

Friedenstein, A. J., Piatetzky-Shapiro, I. I., and Petrakova, K. V. 1966. Osteogenesis in transplants of bone marrow cells. Journal of Embryology and Experimental Morphology 16:581–390.

Friedenstein, A. J., Chailakhyan, R. K., and Gerasimov, U. V. 1987. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinetics 20:263–272.

Gallyamov, A. R., Masgutov, R. F., Rizvanov, A. A., Salafutdinov, I. I., Ahtyamov, I. F., Bogov, A. A. Jr., and Bogov, A. A. 2015. Stromal vascular fraction in peripheral nerve regeneration. International Journal of Developmental Neuroscience 47(A):32.

Gonzalez-Perez, F., Hernández, J., Heimann, C., Phillips, J. B., Udina, E. and Navarro, X. 2018. Schwann cells and mesenchymal stem cells in laminin- or fibronectin aligned matrices and regeneration across a critical size defect of 15 mm in the rat sciatic nerve. Journal of Neurosurgery: Spine 28(1):109–118.

Gronthos, S., Simmons, P. J, Graves, S. E., and Robey, P. G. 2001. Integrin-mediated interactions between human bone marrow stromal precursor cells and the extracellular matrix. Bone (2):174–181.

Jessen, K. R., Mirsky, R., and Lloyd, A. C. 2015. Schwann Cells: Development and Role in Nerve Repair. Cold Spring Harbor Perspectives in Biology 7(7):a020487.

Joseph, N. M., Mukouyama, Y. S., Mosher, J. T., Jaegle, M., Crone, S. A., Dormand, E. L., Lee, K. F., Meijer, D., Anderson, D. J., and Morrison, S. J. 2004. Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development 31:5599–5612.

Kingham, P. J., Kalbermatten, D. F., Mahay, D., Armstrong, S. J., Wiberg, M., and Terenghi, G. 2007. Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Experimental Neurology 207:267–274.

Kopen, G. C., Prockop, D. J., and Phinney, D. G. 1999. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences, U S A 96(19):10711–10716.

Korzhevskii, D. E., Sukhorukova, E. G., Gilerovich, E. G., Petrova, E. S., Kirik, O. V., and Grigor’ev, I. P. 2014. Advantages and disadvantages of zinc-ethanol-formaldehyde as a fixative for immunocytochemical studies and confocal laser microscopy. Neuroscience and Behavioral Physiology 44:542–545.

Lavasani, M., Pollett, J. B., Usas, A., Thompson, S. D., Pollett, A. F., and Huard, J. 2013. The microenvironmentspecific transformation of adult stem cells modelsmalignant triton tumors. PLoS One 8(12):e82173.

Li, Y., Hu, G., and Cheng, Q. 2015. Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges. Frontiers in Medicine 9:20–29.

Li, Z., Qin, H. Feng, Z., Liu, W., Zhou, Y., Yang, L., Zhao, W., and Li, Y. 2013. Human umbilical cord mesenchymal stem cell-loaded amniotic membrane for the repair of radial nerve injury. Neural Regeneration Research 8(36):3441–3448.

Loseva, E. V., Loginova, N. A., Kurskaya, O. V., Podgornyi, O. V., Poltavtseva, R. A., Aleksandrova, M. A., Marei, M. V., Sukhikh, G. T., and Chailakhyan, R. K. 2012. Effects of neurotransplantation of cultured human neural and mesenchymal stem cells on learning and the state of the brain in rats after hypoxia. Neuroscience and Behavioral Physiology 42(5):462–471.

Martin, D. R., Cox, N. R., Hathcock, T. L., Niemeye,r G. P., and Baker, H. J. 2002. Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow. Experimental Hematology 30(8):879–886.

Masgutov, R., Masgutova, G., Mukhametova, L., Garanina, E., Arkhipova, S. S., Zakirova, E., Mukhamedshina, Y. O., Margarita, Z., Gilazieva, Z., Syromiatnikova, V., Mullakhmetova, A., Kadyrova, G., Nigmetzyanova, M., Mikhail, S., Igor, P., Yagudin, R., and Rizvanov, A. 2018. Allogenic adipose derived stem cells transplantation improved sciatic nerve regeneration in rats: autologous nerve graft model. Frontiers in Pharmacology 9:86.

Petrova, E. S. 2015. Injured nerve regeneration using cellbased therapies: current challenges. Acta Naturae 7:38–47.

Petrova E. S. 2018. Potentials to differentiation of mesenchemical stem cells and stimulation of neuroregeneration. Ontogenez 49(4):1–14.

Petrova, E. S., Isaeva, E. N, and Korzhevskii, D. E. 2016. Rat mesenchymal stem cells differentiate to endothelial cells after allotransplantation into the damaged nerve. Transplantation Open 1(1):1–4.

Petrova, E. S., and Isaeva, E. N. 2014. Study of effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve. Biology Bulletin 41:479–485.

Petrova, E. S., Isaeva, E. N., Kolos, E. A., and Korzhevskii, D. E. 2018.Vascularization of the damaged nerve under the effect of experimental cell therapy. Bulletin of Experimental Biology and Medicine 165(1):161–165.

Pitterger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., and Marshak, D. R. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147.

Pulin, A. A., Saburina, I. N., and Repin, V. S. 2008. Surfaces markers of human bone marrow multipotent mesecnhymal stromal cells. Genes and cells 3(3):25–30.

Ribeiro-Resende, V. T., Carrier-Ruiz, A., Lemes, R. M., Reis, R. A., and Mendez-Otero, R. 2012. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system. Molecular Neurodegeneration 7:34.

Shchanitsyn, I. N., Ivanov, A. N., Bazhanov, S. P., Ninel’, V. G., Puchin’jan, D. M., Norkin, I. A. 2017. Stimulation of peripheral nerve regeneration: current status, problems and perspectives. Uspehi fiziologicheskih nauk 48(3):93–112.

Shen, J., Duan, X. H., Cheng, L. N., Zhong, X. M., Guo, R. M., Zhang, F., Zhou, C. P., and Liang, B. L. 2010. In vivo MR imaging tracking of transplanted mesenchymal stem cells in a rabbit model of acute peripheral nerve traction injury. Journal of Magnetic Resonance Imaging 32(5):1076–1085.

Sokolova, I. B., and Polyntsev, D. G. 2017. The efficacy of mesenchymal stem cells for the improvement of cerebral microcirculation in spontaneously hypertensive rats. Cell and Tissue Biology 11(5):343–348.

Southwell, D. G., Nicholas, C. R., Basbaum, A. I., Stryker, M. P., Kriegstein, A. R., Rubenstein, J. L., and Alvarez-Buylla, A. 2014. Interneurons from embryonic development to cell-based therapy. Science 344:1240622.

Stagg, J. and Galipeau, J. 2013. Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation. Current Molecular Medicine 13(5):856–867.

Tamaki, T., Hirata, M., Soeda, S., Nakajima, N., Saito, K., Nakazato, K., Okada, Y., Hashimoto, H., Uchiyama, Y., and Mochida, J. 2014. Preferential and comprehensive reconstitution of severely damaged sciatic nerve using murine skeletal muscle-derived multipotent stem cells. PLoS One 9(3):e91257.

Tohill, M., Mantovani, C., Wiberg, M., and Terenghi, G. 2004. Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neuroscience Letters 362(3):200–203.

Walsh, S. and Midha, R. 2009. Use of stem cells to augment nerve injury repair. Neurosurgery 65:A80–86.

Wislet-Gendebien, S., Hans, G., Leprince, P., Rigo, J. M., Moonen, G., and Rogister, B. 2005. Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 23(3):392–402.

Wong, R. S. 2011. Mesenchymal stem cells: angels or demons? Journal of Biomedicine and Biotechnology 459510:1–8.

Xue, G., He, M., Zhao, J., Chen, Y., Tian, Y., Zhao, B., and Niu, B. 2011. Intravenous umbilical cord mesenchymal stem cell infusion for the treatment ofcombined malnutrition nonunion of the humerus and radial nerve injury. Regenerative Medicine 6(6):733–741.

Yang, J., Lou, Q., Huang, R., Shen, L., and Chen, Z. 2008. Dorsal root ganglion neurons induce transdifferentiation of mesenchymal stem cells along a Schwann cell lineage. Neuroscience Letters 445:246–251.

Yoon, Y. S., Wecker, A., Heyd, L., Park, J. S., Tkebuchava, T., Kusano, K., Hanley, A., Scadova, H., Qin, G., Cha, D. H., Johnson, K. L., Aikawa, R., Asahara, T., and Losordo, D. W. 2005. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. Journal of Clinical Investigation 115(2):326–338.

Zin’kova, N. N., Sokolova, I. B., Viide ,S. K., Shvedova, E. V., Alexandrov, G. V., Kruglyakov, P. V., Polyntsev, D. G., and Gilerovich, E. G. 2007. Mesenchymal stem cell therapy of brain ischemic stroke in rats. Cell and Tissue Biology 1:389–398.

Zhang, P., He, X., Liu, K., Zhao, F., Fu, Z., Zhang, D., Zhang, Q., and Jiang, B. 2004. Bone marrow stromal cells differentiated into functional Schwann cells in injured rats sciatic nerve. Artificial cells, blood substitutes, and immobilization biotechnology 32(4):509–518.

Zochodne, D. W. 2008. Neurobiology of Peripheral Nerve Regeneration. Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, Sao Paulo: Cambridge University Press.
How to Cite
Petrova, E., Isaeva, E., Kolos, E., & Korzhevskii, D. (2018). Allogeneic bone marrow mesenchymal stem cells in the epineurium and perineurium of the recipient rat. Biological Communications, 63(2), 123–132.
Full communications