Immunoregulation Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Xenogeneic Acellular Nerve Grafts Transplant
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This study evaluated whether bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with xenogeneic acellular nerve grafts (xANGs) would reduce the inflammation reaction of xANGs transplantation. BM-MSCs were extracted, separated, purified, and cultured from the bone marrow of rats. Then BM-MSCs were seeded into 5 mm xANGs as experimental group, while xANGs group was chosen as control. Subcutaneous implantation and nerve grafts transplantation were done in this study. Walking-track tests, electrophysiological tests, H&E staining, and immunostaining of CD4, CD8, and CD68 of subcutaneous implantations, cytokine concentrations of IL-2, IL-10, IFN-γ and TNF-α in lymphocytes supernatants and serum of the two groups were evaluated. Walking-track tests and electrophysiological tests suggested the group of BM-MSCs with xANGs obtained better results than xANGs group (P < 0.05). H&E staining and immunostaining of CD4, CD8, and CD68 of subcutaneous implantations showed there were less inflammatory cells in the group of BM-MSCs when compared with the xANGs group. The cytokine concentrations of IL-2, IFN-γ, and TNF-α in BM-MSCs group were lower than xANGs group in lymphocytes supernatants and serum (P < 0.05). However, IL-10 concentrations in BM-MSCs group were higher than xANGs group (P < 0.05). xANG with BM-MSCs showed better nerve repair function when compared with xANG group. Furthermore, xANG with BM-MSCs showed less inflammatory reaction which might indicate the reason of its better nerve regeneration.
KeywordsImmunoregulation Xenogeneic acellular nerve graft Bone marrow-derived mesenchymal stem cells Transplant
We would like to thank the National Natural Science Foundation of China (Grant Nos. 81101363 and 81371944) for financially supporting this study.
Conflict of interest
The authors declare that they have no conflict of interest.
- Bozkurt A, Tholl S, Wehner S, Tank J, Cortese M, Dm O’Dey, Deumens R, Lassner F, Schuegner F, Groeger A, Smeets R, Brook G, Pallua N (2008) Evaluation of functional nerve recovery with Visual-SSI—A novel computerized approach for the assessment of the static sciatic index (SSI). J Neurosci Methods 170(1):117–122PubMedCrossRefGoogle Scholar
- de Menezes Neves PDM, Machado JR, dos Reis MA, Faleiros ACG, de Lima Pereira SA, Rodrigues DBR (2013) Distinct expression of interleukin 17, tumor necrosis factor alpha, transforming growth factor beta, and forkhead box P3 in acute rejection after kidney transplantation. Ann Diagn Pathol 17(1):75–79PubMedCrossRefGoogle Scholar
- Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Keating A, Prockop DJ, Horwitz EM (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317PubMedCrossRefGoogle Scholar
- Friedens AJ, Deriglas UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Rudakow IA (1974) Precursors for fibroblasts in different populations of hematopoietic cells as detected by invitro colony assay method. Exp Hematol 2(2):83–92Google Scholar
- He B, Zhu QT, Chai YM, Ding XH, Tang JY, Gu LQ, Xiang JP, Yang YX, Zhu JK, Liu XL (2012) Outcomes with the use of human acellular nerve graft for repair of digital nerve defects: a prospective, multicenter, controlled clinical trial. J Tissue Eng Reg Med 6:76Google Scholar
- Luz-Crawford P, Kurte M, Bravo-Alegria J, Contreras R, Nova-Lamperti E, Tejedor G, Noel D, Jorgensen C, Figueroa F, Djouad F, Carrion F (2013) Mesenchymal stem cells generate a CD4(+) CD25(+) Foxp3(+) regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther 4:65PubMedPubMedCentralCrossRefGoogle Scholar
- Mandegary A, Azmandian J, Soleymani S, Pootari M, Habibzadeh S-D, Ebadzadeh M-R, Dehghani-Firouzabadi M-H (2013) Effect of donor tumor necrosis factor-alpha and interleukin-10 genotypes on delayed graft function and acute rejection in kidney transplantation. Iran J Kidney Dis 7(2):135–141PubMedGoogle Scholar
- Nagler A, Berger R, Ackerstein A, Czyz JA, Luis Diez-Martin J, Naparstek E, Or R, Gan S, Shimoni A, Slavin S (2010) A randomized controlled multicenter study comparing recombinant interleukin 2 (rIL-2) in conjunction with recombinant interferon alpha (IFN-alpha) versus no immunotherapy for patients with malignant lymphoma postautologous stem cell transplantation. J Immunother 33(3):326–333PubMedCrossRefGoogle Scholar
- Polchert D, Sobinsky J, Douglas GW, Kidd M, Moadsiri A, Reina E, Genrich K, Mehrotra S, Setty S, Smith B, Bartholomew A (2008) IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol 38(6):1745–1755PubMedPubMedCentralCrossRefGoogle Scholar
- Rendina M, Castellaneta NM, Fagiuoli S, Ponziani FR, Vigano R, Iemmolo RM, Donato MF, Toniutto P, Pasulo L, Morelli MC, Burra P, Miglioresi L, Giannelli V, Di Paolo D, Di Leo A (2011) Acute and chronic rejection during interferon therapy in HCV recurrent liver transplant patients: results from the AISF-RECOLT-C group. Digest Liver Dis 43:S148–S149Google Scholar