Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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T Lymphocyte Subsets and Cytokines in Rats Transplanted with Adipose-Derived Mesenchymal Stem Cells and Acellular Nerve for Repairing the Nerve Defects

  • Jiang, Liang-fu (Department of Hand & Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University) ;
  • Chen, Ou (Department of Orthopaedics, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine) ;
  • Chu, Ting-gang (Department of Hand & Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University) ;
  • Ding, Jian (Department of Hand & Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University) ;
  • Yu, Qing (Department of Hand & Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University)
  • Received : 2014.12.19
  • Accepted : 2015.03.23
  • Published : 2015.08.28
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Abstract

Objective : The aim of this study was to explore the immunity in rats transplanted with adipose-derived mesenchymal stem cells (ADSCs) and acellular nerve (ACN) for repairing sciatic nerve defects. Methods : ADSCs were isolated from the adipose tissues of Wistar rats. Sprague-Dawley rats were used to establish a sciatic nerve defect model and then divided into four groups, according to the following methods : Group A, allogenic nerve graft; Group B, allograft with ACN; Group C, allograft ADSCs+ACN, and Group D, nerve autograft. Results : At the day before transplantation and 3, 7, 14, and 28 days after transplantation, orbital venous blood of the Sprague-Dawley rats in each group was collected to detect the proportion of $CD3^+$, $CD4^+$, and $CD8^+$ subsets using flow cytometry and to determine the serum concentration of interleukin-2 (IL-2), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and $interferon-{\gamma}$ ($IFN-{\gamma}$) using enzyme-linked immunosorbent assay (ELISA). At each postoperative time point, the proportion of $CD3^+$, $CD4^+$, and $CD8^+$ subsets and the serum concentration of IL-2, $TNF-{\alpha}$, and $IFN-{\gamma}$ in group C were all near to those in group B and group D, in which no statistically significant difference was observed. As compared with group A, the proportion of $CD3^+$, $CD4^+$, and $CD8^+$ subsets and the serum concentration of IL-2, $TNF-{\alpha}$, and $IFN-{\gamma}$ were significantly reduced in group C (p<0.05). Conclusion : The artificial nerve established with ADSCs and ACN has no obvious allograft rejection for repairing rat nerve defects.

Keywords

References

  1. Bain JR, Mackinnon SE, Hudson AR, Falk RE, Falk JA, Hunter DA : The peripheral nerve allograft : an assessment of regeneration across nerve allografts in rats immunosuppressed with cyclosporin A. Plast Reconstr Surg 82 : 1052-1066, 1988 https://doi.org/10.1097/00006534-198812000-00019
  2. Comoli P, Ginevri F, Maccario R, Avanzini MA, Marconi M, Groff A, et al. : Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant 23 : 1196-1202, 2008
  3. de Ruiter GC, Spinner RJ, Yaszemski MJ, Windebank AJ, Malessy MJ : Nerve tubes for peripheral nerve repair. Neurosurg Clin N Am 20 : 91-105, vii, 2009 https://doi.org/10.1016/j.nec.2008.08.001
  4. Gao X, Wang Y, Chen J, Peng J : The role of peripheral nerve ECM components in the tissue engineering nerve construction. Rev Neurosci 24 : 443-453, 2013
  5. Hong SJ, Traktuev DO, March KL : Therapeutic potential of adipose-derived stem cells in vascular growth and tissue repair. Curr Opin Organ Transplant 15 : 86-91, 2010 https://doi.org/10.1097/MOT.0b013e328334f074
  6. Hudson TW, Zawko S, Deister C, Lundy S, Hu CY, Lee K, et al. : Optimized acellular nerve graft is immunologically tolerated and supports regeneration. Tissue Eng 10 : 1641-1651, 2004 https://doi.org/10.1089/ten.2004.10.1641
  7. Jiang L, Zhu JK, Liu XL, Xiang P, Hu J, Yu WH : Differentiation of rat adipose tissue-derived stem cells into Schwann-like cells in vitro. Neuroreport 19 : 1015-1019, 2008 https://doi.org/10.1097/WNR.0b013e3283040efc
  8. Kang HG, Zhang D, Degauque N, Mariat C, Alexopoulos S, Zheng XX : Effects of cyclosporine on transplant tolerance : the role of IL-2. Am J Transplant 7 : 1907-1916, 2007 https://doi.org/10.1111/j.1600-6143.2007.01881.x
  9. Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G : Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol 207 : 267-274, 2007 https://doi.org/10.1016/j.expneurol.2007.06.029
  10. Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, et al. : T cell responses to allogeneic human mesenchymal stem cells : immunogenicity, tolerance, and suppression. J Biomed Sci 12 : 47-57, 2005 https://doi.org/10.1007/s11373-004-8183-7
  11. Kuo YR, Chen CC, Goto S, Lee IT, Huang CW, Tsai CC, et al. : Modulation of immune response and T-cell regulation by donor adipose-derived stem cells in a rodent hind-limb allotransplant model. Plast Reconstr Surg 128 : 661e-672e, 2011 https://doi.org/10.1097/PRS.0b013e318230c60b
  12. Kvist M, Sondell M, Kanje M, Dahlin LB : Regeneration in, and properties of, extracted peripheral nerve allografts and xenografts. J Plast Surg Hand Surg 45 : 122-128, 2011 https://doi.org/10.3109/2000656X.2011.571847
  13. Lin CS, Lin G, Lue TF : Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev 21 : 2770-2778, 2012 https://doi.org/10.1089/scd.2012.0176
  14. Liu GB, Cheng YX, Feng YK, Pang CJ, Li Q, Wang Y, et al. : Adipose-derived stem cells promote peripheral nerve repair. Arch Med Sci 7 : 592-596, 2011
  15. Mackinnon SE, Doolabh VB, Novak CB, Trulock EP : Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg 107 : 1419-1429, 2001 https://doi.org/10.1097/00006534-200105000-00016
  16. Marconi S, Castiglione G, Turano E, Bissolotti G, Angiari S, Farinazzo A, et al. : Human adipose-derived mesenchymal stem cells systemically injected promote peripheral nerve regeneration in the mouse model of sciatic crush. Tissue Eng Part A 18 : 1264-1272, 2012 https://doi.org/10.1089/ten.tea.2011.0491
  17. Rovak JM, Bishop DK, Boxer LK, Wood SC, Mungara AK, Cederna PS : Peripheral nerve transplantation : the role of chemical acellularization in eliminating allograft antigenicity. J Reconstr Microsurg 21 : 207-213, 2005 https://doi.org/10.1055/s-2005-869828
  18. Santiago LY, Clavijo-Alvarez J, Brayfield C, Rubin JP, Marra KG : Delivery of adipose-derived precursor cells for peripheral nerve repair. Cell Transplant 18 : 145-158, 2009 https://doi.org/10.3727/096368909788341289
  19. Sioud M, Mobergslien A, Boudabous A, Floisand Y : Evidence for the involvement of galectin-3 in mesenchymal stem cell suppression of allogeneic T-cell proliferation. Scand J Immunol 71 : 267-274, 2010 https://doi.org/10.1111/j.1365-3083.2010.02378.x
  20. Sondell M, Lundborg G, Kanje M : Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction. Brain Res 795 : 44-54, 1998 https://doi.org/10.1016/S0006-8993(98)00251-0
  21. Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M : Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24 : 74-85, 2006 https://doi.org/10.1634/stemcells.2004-0359
  22. Sun XH, Che YQ, Tong XJ, Zhang LX, Feng Y, Xu AH, et al. : Improving nerve regeneration of acellular nerve allografts seeded with SCs bridging the sciatic nerve defects of rat. Cell Mol Neurobiol 29 : 347-353, 2009 https://doi.org/10.1007/s10571-008-9326-6
  23. Tung TH, Mohanakumar T, Mackinnon SE : TH1/TH2 cytokine profile of the immune response in limb component transplantation. Plast Reconstr Surg 116 : 557-566, 2005 https://doi.org/10.1097/01.prs.0000172888.45875.66
  24. Velasquez SY, García LF, Opelz G, Alvarez CM, Susal C : Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-$\gamma$ and IL-2. Transplantation 96 : 154-161, 2013 https://doi.org/10.1097/TP.0b013e318296fd69
  25. Wang Y, Zhao Z, Ren Z, Zhao B, Zhang L, Chen J, et al. : Recellularized nerve allografts with differentiated mesenchymal stem cells promote peripheral nerve regeneration. Neurosci Lett 514 : 96-101, 2012 https://doi.org/10.1016/j.neulet.2012.02.066
  26. Yu X, Jiang Y, Lu L, Gong X, Sun X, Xuan Z, et al. : A crucial role of IL-17 and IFN-$\gamma$ during acute rejection of peripheral nerve xenotransplantation in mice. PLoS One 7 : e34419, 2012 https://doi.org/10.1371/journal.pone.0034419
  27. Zhang Y, Luo H, Zhang Z, Lu Y, Huang X, Yang L, et al. : A nerve graft constructed with xenogeneic acellular nerve matrix and autologous adipose-derived mesenchymal stem cells. Biomaterials 31 : 5312-5324, 2010 https://doi.org/10.1016/j.biomaterials.2010.03.029
  28. Zimmerer JM, Horne PH, Fiessinger LA, Fisher MG, Pham TA, Saklayen SL, et al. : Cytotoxic effector function of CD4-independent, CD8(+) T cells is mediated by TNF-$\alpha$/TNFR. Transplantation 94 : 1103-1110, 2012

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