Abstract
Our previous study has showed that co-grafted Schwann cells (SCs) promote proliferation and migration of the grafted oligodendrocyte precursor cells (OPCs). However, how the co-grafted SCs affect OPCs has not been clarified. In the present study, we confirmed that SC-induced proliferation and migration of OPCs were mediated by SC-secreted factors using SC-conditioned medium (SCM). Then, we detected several candidate factors, PDGF-AA, FGF-2, and IGF-1, in SCs and SCM, and their receptors in OPCs. Finally, by using the selective inhibitors, the effects of these candidate factors on proliferation and migration of OPCs were examined. Our results showed that SCM-stimulated proliferation and migration of OPCs could be markedly decreased by both AG1295 (the inhibitor of PDGFR) and PD173074 (the inhibitor of FGFR). Together, our study suggests that SCs affect proliferation and migration of OPCs through secreting PDGF-AA and FGF-2. Identity of these molecules not only contributes to understand the mechanism of SC-induced proliferation and migration of OPCs but also provides possible target for treatment of CNS diseases.
Similar content being viewed by others
References
Acheson A, Barker PA, Alderson RF, Miller FD, Murphy RA (1991) Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: inhibition by antibodies to NGF. Neuron 7:265–275
Banai S, Wolf Y, Golomb G, Pearle A, Waltenberger J, Fishbein I, Schneider A, Gazit A, Perez L, Huber R, Lazarovichi G, Rabinovich L, Levitzki A, Gertz SD (1998) PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine. Circulation 97:1960–1969
Bandtlow CE, Heumann R, Schwab ME, Thoenen H (1987) Cellular localization of nerve growth factor synthesis by in situ hybridization. EMBO J 6:891–899
Baumann N, Pham-Dinh D (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81:871–927
Cai F, Campana WM, Tomlinson DR, Fernyhough P (1999) Transforming growth factor-beta1 and glial growth factor 2 reduce neurotrophin-3 mRNA expression in cultured Schwann cells via a cAMP-dependent pathway. Brain Res Mol Brain Res 71:256–264
Chau CH, Shum DK, Li H, Pei J, Lui YY, Wirthlin L, Chan YS, Xu XM (2004) Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury. FASEB J Off Publ Fed Am Soc Exp Biol 18:194–196
Cui QL, Almazan G (2007) IGF-I-induced oligodendrocyte progenitor proliferation requires PI3K/Akt, MEK/ERK, and Src-like tyrosine kinases. J Neurochem 100:1480–1493
Ding Y, Yan Q, Ruan JW, Zhang YQ, Li WJ, Zeng X, Huang SF, Zhang YJ, Wang S, Dong H, Zeng YS (2011) Bone marrow mesenchymal stem cells and electroacupuncture downregulate the inhibitor molecules and promote the axonal regeneration in the transected spinal cord of rats. Cell Transplant 20:475–491
Feron F, Perry C, Cochrane J, Licina P, Nowitzke A, Urquhart S, Geraghty T, Mackay-Sim A (2005) Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain J Neurol 128:2951–2960
Fok-Seang J, Mathews GA, FFrench-Constant C, Trotter J, Fawcett JW (1995) Migration of oligodendrocyte precursors on astrocytes and meningeal cells. Dev Biol 171:1–15
Givogri MI, Galbiati F, Fasano S, Amadio S, Perani L, Superchi D, Morana P, Del Carro U, Marchesini S, Brambilla R, Wrabetz L, Bongarzone E (2006) Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophy. J Neurosci Off J Soc Neurosci 26:3109–3119
Harrison B (1985) Schwann cell and oligodendrocyte remyelination in lysolecithin-induced lesions in irradiated rat spinal cord. J Neurol Sci 67:143–159
Hu JG, Fu SL, Zhang KH, Li Y, Yin L, Lu PH, Xu XM (2004) Differential gene expression in neural stem cells and oligodendrocyte precursor cells: a cDNA microarray analysis. J Neurosci Res 78:637–646
Hu J, Deng L, Wang X, Xu XM (2009) Effects of extracellular matrix molecules on the growth properties of oligodendrocyte progenitor cells in vitro. J Neurosci Res 87:2854–2862
Hu JG, Wang XF, Deng LX, Liu NK, Gao X, Chen JH, Zhou FC, Xu XM (2013) Cotransplantation of glial restricted precursor cells and Schwann cells promotes functional recovery after spinal cord injury. Cell Transplant 22:2219–2236
Kodelja V, Muller C, Tenorio S, Schebesch C, Orfanos CE, Goerdt S (1997) Differences in angiogenic potential of classically vs alternatively activated macrophages. Immunobiology 197:478–493
Lee JC, Mayer-Proschel M, Rao MS (2000) Gliogenesis in the central nervous system. Glia 30:105–121
Luk F, Yu Y, Walsh WR, Yang JL (2011) IGF1R-targeted therapy and its enhancement of doxorubicin chemosensitivity in human osteosarcoma cell lines. Cancer Invest 29:521–532
Ma Z, Cao Q, Zhang L, Hu J, Howard RM, Lu P, Whittemore SR, Xu XM (2009) Oligodendrocyte precursor cells differentially expressing Nogo-A but not MAG are more permissive to neurite outgrowth than mature oligodendrocytes. Exp Neurol 217:184–196
Ma YH, Zhang Y, Cao L, Su JC, Wang ZW, Xu AB, Zhang SC (2010) Effect of neurotrophin-3 genetically modified olfactory ensheathing cells transplantation on spinal cord injury. Cell Transplant 19:167–177
McDermott U, Ames RY, Iafrate AJ, Maheswaran S, Stubbs H, Greninger P, McCutcheon K, Milano R, Tam A, Lee DY, Lucien L, Brannigan BW, Ulkus LE, Ma XJ, Erlander MG, Haber DA, Sharma SV, Settleman J (2009) Ligand-dependent platelet-derived growth factor receptor (PDGFR)-alpha activation sensitizes rare lung cancer and sarcoma cells to PDGFR kinase inhibitors. Cancer Res 69:3937–3946
Milner R, Anderson HJ, Rippon RF, McKay JS, Franklin RJ, Marchionni MA, Reynolds R, Ffrench-Constant C (1997) Contrasting effects of mitogenic growth factors on oligodendrocyte precursor cell migration. Glia 19:85–90
Miyamoto Y, Yamauchi J, Tanoue A (2008) Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn. J Neurosci Off J Soc Neurosc 28:8326–8337
Morrissey TK, Kleitman N, Bunge RP (1991) Isolation and functional characterization of Schwann cells derived from adult peripheral nerve. J Neurosci Off J Soc Neurosci 11:2433–2442
Neuberger TJ, De Vries GH (1993) Distribution of fibroblast growth factor in cultured dorsal root ganglion neurons and Schwann cells. I Localization during maturation in vitro. J Neurocytol 22:436–448
Oudega M, Xu XM (2006) Schwann cell transplantation for repair of the adult spinal cord. J Neurotrauma 23:453–467
Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B, Lemoine NR, Stamp GW, Aboagye EO, Seckl MJ (2009) The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res 69:8645–8651
Raff MC, Miller RH, Noble M (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303:390–396
Rao MS, Mayer-Proschel M (2000) Precursor cells for transplantation. Prog Brain Res 128:273–292
Springer JE, Mu X, Bergmann LW, Trojanowski JQ (1994) Expression of GDNF mRNA in rat and human nervous tissue. Exp Neurol 127:167–170
Vora P, Pillai PP, Zhu W, Mustapha J, Namaka MP, Frost EE (2011) Differential effects of growth factors on oligodendrocyte progenitor migration. Eur J Cell Biol 90:649–656
Xu XM, Martin GF (1989) Developmental plasticity of the rubrospinal tract in the North American opossum. J Comp Neurol 279:368–381
Xu XM, Onifer SM (2009) Transplantation-mediated strategies to promote axonal regeneration following spinal cord injury. Respir Physiol Neurobiol 169:171–182
Xu XM, Guenard V, Kleitman N, Bunge MB (1995) Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 351:145–160
Xu XM, Chen A, Guenard V, Kleitman N, Bunge MB (1997) Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. J Neurocytol 26:1–16
Zha J, Smith A, Andreansky S, Bracchi-Ricard V, Bethea JR (2014) Chronic thoracic spinal cord injury impairs CD8+ T-cell function by up-regulating programmed cell death-1 expression. J Neuroinflammation 11:65
Acknowledgments
This work was supported by the National Natural Science Foundation of China (nos. 81171465 and 81471277).
Conflict of Interest
None.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Yue-Juan Chen and Jing-Xing Zhang contributed equally to this work.
Rights and permissions
About this article
Cite this article
Chen, YJ., Zhang, JX., Shen, L. et al. Schwann cells induce Proliferation and Migration of Oligodendrocyte Precursor Cells Through Secretion of PDGF-AA and FGF-2. J Mol Neurosci 56, 999–1008 (2015). https://doi.org/10.1007/s12031-015-0570-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-015-0570-1