Research Article
Bone marrow- and adipose-derived stem cells show expression of myelin mRNAs and proteins
Published Online:10 May 2010https://doi.org/10.2217/rme.10.15
Abstract
Aims: PNS myelin is formed by Schwann cells (SCs). In this study, we applied an in vitro model to study myelin formation, using bone marrow mesenchymal stem cells and adipose-derived stem cells differentiated into SC-like cells and co-cultured with dissociated adult dorsal root ganglia neurons. Methods: Immunocytochemistry, reverse transcription-PCR and western blotting techniques were used to investigate the expression of myelin proteins at both the transcriptional and translational level. Results: Transcripts for protein zero, peripheral myelin protein 22 and myelin basic protein were detected in differentiated stem cells following co-culture with neuronal cells. Furthermore, protein zero, peripheral myelin protein 22 and myelin basic proteins were recognized in the co-cultures. These results were consistent with immunostaining of myelin proteins and with observation by electron microscopy. Conclusion: Both types of adult stems cells differentiated into SC-like cells have potential to myelinate neuronal cells during regeneration, being functionally identical to SCs of the PNS.
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Bibliography
- 1 Snipes GJ, Suter U, Welcher AA, Shooter EM: Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13). J. Cell Biol.117,225–238 (1992).
- 2 Schachner M, Bartsch U: Multiple functions of the myelin-associated glycoprotein MAG (siglec-4a) in formation and maintenance of myelin. Glia29,154–165 (2000).
- 3 Quarles RH: Glycoproteins of myelin sheaths. J. Mol. Neurosci.8,1–12 (1997).
- 4 Pareek S, Suter U, Snipes GJ et al.: Detection and processing of peripheral myelin protein PMP-22 in cultured Schwann cells. J. Biol. Chem.268,10372–10379 (1993).
- 5 Greenfield S, Weise MJ, Gantt G et al.: Basic proteins of rodent peripheral nerve myelin: immunochemical identification of the 21.5K, 18.5K, 17K, 14K, and P2 proteins. J. Neurochem.39,1278–1282 (1982).
- 6 Snipes GJ, Suter U: Molecular anatomy and genetics of myelin proteins in the peripheral nervous system. J. Anat.186(3),483–494 (1995).
- 7 Yin Q, Kemp GJ, Yu LG et al.: Expression of Schwann cell-specific proteins and low-molecular-weight neurofilament protein during regeneration of sciatic nerve treated with neurotrophin-4. Neuroscience105,779–783 (2001).
- 8 Yin X, Crawford TO, Griffin JW et al.: Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons. J. Neurosci.18,1953–1962 (1998).
- 9 Caddick J, Kingham PJ, Gardiner NJ et al.: Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage. Glia54,840–849 (2006).
- 10 Tohill M, Terenghi G: Stem-cell plasticity and therapy for injuries of the peripheral nervous system. Biotechnol. Appl. Biochem.40,17–24 (2004).
- 11 Kingham PJ, Kalbermatten DF, Mahay D et al.: Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp. Neurol.207,267–274 (2007).
- 12 Mahay D, Terenghi G, Shawcross SG: Growth factors in mesenchymal stem cells following glial cell differentiation. Biotechnol. Appl. Biochem.51,167–176 (2008).
- 13 Martini R: Introduction to myelin formation and maintenance. Microsc. Res. Tech.41,341–343 (1998).
- 14 Yang J, Lou Q, Huang R et al.: Dorsal root ganglion neurons induce transdifferentiation of mesenchymal stem cells along a Schwann cell lineage. Neurosci. Lett.445,246–251 (2008).
- 15 Brockes JP, Fields KL, Raff MC: Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Res.165,105–118 (1979).
- 16 Mosahebi A, Simon M, Wiberg M, Terenghi G: A novel use of alginate hydrogel as Schwann cell matrix. Tissue Eng.7,525–534 (2001).
- 17 Mahay D, Terenghi D, Shawcross SG: Schwann cell mediated trophic effects by differentiated mesenchymal stem cells. Exp. Cell Res.314,2692–2701 (2008).
- 18 Keilhoff G, Stang F, Goihl A et al.: Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination. Cell. Mol. Neurobiol.26,1235–1252 (2006).
- 19 Obremski VJ, Bunge MB: Addition of purified basal lamina molecules enables Schwann cell ensheathment of sympathetic neurites in culture. Dev. Biol.168,124–137 (1995).
- 20 Choi KC, Yoo DS, Cho KS et al.: Effect of single growth factor and growth factor combinations on differentiation of neural stem cells. J. Korean Neurosurg. Soc.44,375–381 (2008).
- 21 Jessen KR, Mirsky R: Schwann cells and their precursors emerge as major regulators of nerve development. Trends Neurosci.22,402–410 (1999).
- 22 Fernandez R, Pena E, Navascues J et al.: cAMP-dependent reorganization of the Cajal bodies and splicing machinery in cultured Schwann cells. Glia40,378–388 (2002).
- 23 D’Urso D, Ehrhardt P, Muller HW: Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. J. Neurosci.19,3396–3403 (1999).
- 24 Shine HD, Readhead C, Popko B et al.: Morphometric analysis of normal, mutant, and transgenic CNS: correlation of myelin basic protein expression to myelinogenesis. J. Neurochem.58,342–349 (1992).
- 25 Martini R, Schachner M: Molecular bases of myelin formation as revealed by investigations on mice deficient in glial cell surface molecules. Glia19,298–310 (1997).
- 26 Niemann S, Sereda MW, Suter U et al.: Uncoupling of myelin assembly and schwann cell differentiation by transgenic overexpression of peripheral myelin protein 22. J. Neurosci.20,4120–4128 (2000).
- 27 Segovia J, Lawless GM, Tillakaratne NJK et al.: Cyclic AMP decreases the expression of a neuronal marker (GAD67) and increases the expression of an astroglial marker (GFAP) in C6 cells. J. Neurochem.63,1218–1225 (1994).
