摘要 Objectives: Currently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regeneration and restoration at peripheral nerve injury sites. Methods: In this study, adipose tissue-derived stem cells were induced to differentiate into neural progenitor cells, transfected with a green fluorescent protein-containing lentivirus, and then transplanted into the lesions of rats with sciatic nerve compression injury. Results: Fluorescence microscopy revealed that the transplanted cells survived, migrated, and differentiated in rats. At two weeks post-operation, a large number of transplanted cells had migrated to the injured lesions; at six weeks post-operation, transplanted cells were visible around the injured nerve and several cells were observed to express a Schwann cell marker. Sciatic function index and electrophysiological outcomes of the transplantation group were better than those of the control group. Cell transplantation promoted the recovery of motor nerve conduction velocity and compound muscle action potential amplitude, and reduced gastrocnemius muscle atrophy. Conclusions: Our experimental findings indicate that neural progenitor cells, differentiated from adipose tissue-derived stem cells, are potential seed stem cells that can be transplanted into lesions to treat sciatic nerve injury. This provides a theoretical basis for their use in clinical applications.
Abstract: Objectives: Currently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regeneration and restoration at peripheral nerve injury sites. Methods: In this study, adipose tissue-derived stem cells were induced to differentiate into neural progenitor cells, transfected with a green fluorescent protein-containing lentivirus, and then transplanted into the lesions of rats with sciatic nerve compression injury. Results: Fluorescence microscopy revealed that the transplanted cells survived, migrated, and differentiated in rats. At two weeks post-operation, a large number of transplanted cells had migrated to the injured lesions; at six weeks post-operation, transplanted cells were visible around the injured nerve and several cells were observed to express a Schwann cell marker. Sciatic function index and electrophysiological outcomes of the transplantation group were better than those of the control group. Cell transplantation promoted the recovery of motor nerve conduction velocity and compound muscle action potential amplitude, and reduced gastrocnemius muscle atrophy. Conclusions: Our experimental findings indicate that neural progenitor cells, differentiated from adipose tissue-derived stem cells, are potential seed stem cells that can be transplanted into lesions to treat sciatic nerve injury. This provides a theoretical basis for their use in clinical applications.
基金资助: Supported by the National Natural Science Foundation of China (Nos. 81171089 and 81471201) and the Scientific and Technological Projects of Wuhan City of China (No. 2013060602010240).
通讯作者:
Yang Hu,E-mail:huyang081991@126.com;Zhouping Tang,E-mail:ddjtzp@163.com
E-mail: huyang081991@126.com;ddjtzp@163.com
引用本文:
Shasha Dong Na Liu Yang Hu, Ping Zhang, Chao Pan, Youping Zhang, Yingxin Tang, Zhouping Tang. Transplantation of neural progenitor cells differentiated from adipose tissue-derived stem cells for treatment of sciatic nerve injury[J]. 临床转化神经科学, 2016, 2(2): 108-119.
Shasha Dong Na Liu Yang Hu, Ping Zhang, Chao Pan, Youping Zhang, Yingxin Tang, Zhouping Tang. Transplantation of neural progenitor cells differentiated from adipose tissue-derived stem cells for treatment of sciatic nerve injury. Translational Neuroscience and Clinics, 2016, 2(2): 108-119.
[1] Terenghi G. Peripheral nerve regeneration and neurotrophic factors. J Anat 1999, 194(Pt 1):1-14.
[2] Berrocal YA, Almeida VW, Gupta R, Levi AD. Transplanta-tion of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats. J Neurosurg 2013, 119:720-732.
[3] Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002, 13:4279-4295.
[4] Faroni A, Terenghi G, Magnaghi V. Expression of functional gamma-aminobutyric acid type A receptors in Schwann-like adult stem cells. J Mol Neurosci 2012, 47:619-630.
[5] Kalbermatten DF, Schaakxs D, Kingham PJ, Wiberg M. Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat. Cell Tissue Res 2011, 344:251-260.
[6] Gimble JM, Guilak F. Differentiation potential of adipose derived adult stem (ADAS) cells. Curr Top Dev Biol 2003, 58:137-160.
[7] Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res 2007, 100:1249-1260.
[8] Tobita M, Mizuno H. Adipose-derived stem cells and periodontal tissue engineering. Int J Oral Max Impl 2013, 28:e487-e493.
[9] Liu G, Cheng Y, Guo S, Feng Y, Li Q, Jia H, Wang Y, Tong L, Tong X. Transplantation of adipose-derived stem cells for peripheral nerve repair. Int J Mol Med 2011, 28:565-572.
[10] Kim EH, Heo CY. Current applications of adipose-derived stem cells and their future perspectives. World J Stem Cells 2014, 6:65-68.
[11] Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 2007, 327:449-462.
[12] Zhang Y, Liu N, Tang Y, Yang E, Dong S, Huang M, Pan C, Zhang Y, Zhang P, Chen H, et al. Efficient generation of neural stem cell-like cells from rat adipose derived stem cells after lentiviral transduction with green fluorescent protein. Mol Neurobiol 2014, 50:647-654.
[13] Nagase T, Matsumoto D, Nagase M, Yoshimura K, Shigeura T, Inoue M, Hasegawa M, Yamagishi M, Machida M. Neurospheres from human adipose tissue transplanted into cultured mouse embryos can contribute to craniofacial morphogenesis:A preliminary report. J Craniofac Surg 2007, 18:49-53.
[14] Xu Y, Liu Z, Liu L, Zhao C, Xiong F, Zhou C, Li Y, Shan Y, Peng F, Zhang C. Neurospheres from rat adipose-derived stem cells could be induced into functional Schwann cell-like cells in vitro. BMC Neurosci 2008, 9:21.
[15] Safford KM, Safford SD, Gimble JM, Shetty AK, Rice HE. Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells. Exp Neurol 2004, 187:319-328.
[16] Safford KM, Hicok KC, Safford SD, Halvorsen YD, Wilkison WO, Gimble JM, Rice HE. Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun 2002, 294:371-379.
[17] Santiago LY, Clavijo-Alvarez J, Brayfield C, Rubin JP, Marra KG. Delivery of adipose-derived precursor cells for peripheral nerve repair. Cell Transplant 2009, 18:145-158.
[18] 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 2007, 207:267-274.
[19] Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K. Glial differentiation of human adipose-derived stem cells:Implications for cell-based transplantation therapy. Neuroscience 2013, 236:55-65.
[20] Nachum MD, Melamed E, Offen D. Stem cells treatment for sciatic nerve injury. Expert Opin Biol Ther 2011, 12:1591-1597.
[21] Kanno H. Regenerative therapy for neuronal diseases with transplantation of somatic stem cells. World J Stem Cells 2013, 5:163-171.
[22] Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue:Implications for cell-based therapies. Tissue Eng 2001, 7:211-228.
[23] Mohammadi R, Azizi S, Amini K. Effects of undifferentiated cultured omental adipose-derived stem cells on peripheral nerve regeneration. J Surg Res 2013, 180:e91-e97.
[24] Kolle SF, Fischer-Nielsen A, Mathiasen AB, Elberg JJ, Oliveri RS, Glovinski PV, Kastrup J, Kirchhoff M, Rasmussen BS, Talman ML, et al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival:A randomised placebo-controlled trial. Lancet 2013, 382:1113-1120.
[25] Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, Kim YJ, Jo JY, Yoon EJ, Choi HJ, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 2011, 20:1297-1308.
[26] Yang KL, Lee JT, Pang CY, Lee TY, Chen SP, Liew HK, Chen SY, Chen TY, Lin PY. Human adipose-derived stem cells for the treatment of intracerebral hemorrhage in rats via femoral intravenous injection. Cell Mol Biol Lett 2012, 17:376-392.
[27] Chen J, Tang YX, Liu YM, Chen J, Hu XQ, Liu N, Wang SX, Zhang Y, Zeng WG, Ni HJ, et al. Transplantation of adipose-derived stem cells is associated with neural differentiation and functional improvement in a rat model of intracerebral hemorrhage. CNS Neurosci Ther 2012, 18:847-854.
[28] Chung JY, Kim W, Im W, Yoo DY, Choi JH, Hwang IK, Won MH, Chang IB, Cho BM, Hwang HS, Moon SM. Neuroprotective effects of adipose-derived stem cells against ischemic neuronal damage in the rabbit spinal cord. J Neurol Sci 2012, 317(1-2):40-46.
[29] Lattanzi W, Geloso MC, Saulnier N, Giannetti S, Puglisi MA, Corvino V, Gasbarrini A, Michetti F. Neurotrophic features of human adipose tissue-derived stromal cells:In vitro and in vivo studies. J Biomed Biotechnol 2011, 2011:468705.
[30] Kingham PJ, Kolar MK, Novikova LN, Novikov LN, Wiberg M. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair. Stem Cells Dev 2013, 23(7):741-754.
2016, Vol. 2 
