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Transformation of human umbilical mesenchymal cells into neurons in vitro

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Neuronal transplantation has provided a promising approach for treating neurodegenerative diseases. Recently, efforts have been directed at in vitro induction of various stem cells to transform into neurons. We report the first successful quantities in an in vitro attempt at directing the transformation into neurons of human umbilical mesenchymal cells, which are capable of rapid proliferation in vitro and are easily available. When cultured in neuronal conditioned medium, human umbilical mesenchymal cells started to express neuron-specific proteins such as NeuN and neurofilament (NF) on the 3rd day and exhibited retraction of the cell body, elaboration of processes, clustering of cells and expression of functional mRNA responsible for the synthesis of subunits of the kainate receptor and glutamate decarboxylase on the 6th day. Between the 9th and 12th days, the percentage of human umbilical mesenchymal cells expressing NF was as high as 87%, while functionality was demonstrated by glutamate invoking an inward current. At this stage, cells were differentiated into mature neurons in the postmitosis phase.

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References

  1. Arsenijevic Y, Weiss S. Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: Distinct actions from those of brain-derived neurotrophic factor. J Neurosci 18:2118–2128;1998.

    Google Scholar 

  2. Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ. Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats — similarities to astrocyte grafts. Proc Natl Acad Sci USA 95:3908–3913;1998.

    Google Scholar 

  3. Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Von Zastrow M, Beattie MS, Malenka RC. Control of synaptic strength by glial TNFα. Science 295:2282–2285;2002.

    Google Scholar 

  4. Cameron HA, Woolley CS, McEwen BS, Gould E. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344;1993.

    Google Scholar 

  5. Cao QL, Zhang YP, Howard RM, Walters WM, Tsoulfas P, Whittemore SR. Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage. Exp Neurol 167:48–58;2001.

    Google Scholar 

  6. Forraz N, Pettengell R, McGuckin CP. Hematopoietic and neuroglial progenitors are promoted during cord blood ex vivo expansion. Br J Haematol 119:888;2002.

    Google Scholar 

  7. Fraichard A, Chassande O, Bilbaut G, Dehay C, Savatier P, Samarut J. In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J Cell Sci 108:3181–3188;1995.

    Google Scholar 

  8. Gerhardt GA, Cass WA, Huettl PO, Brock S, Zhang Z, Gash DM. GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys. Brain Res 817:163–171;1999.

    Google Scholar 

  9. Ha Y, Choi JU, Yoon DH, Yeon DS, Lee JJ, Kim HO, Cho YE. Neural phenotype expression of cultured human cord blood cells in vitro. Neuroreport 12:3523–3527;2001.

    Google Scholar 

  10. Hendrickson AE, Van Brederode JF, Mulligan KA, Celio MR. Development of the calcium-binding protein parvalbumin and calbindin in monkey striate cortex. J Comp Neurol 307:626–646;1991.

    Google Scholar 

  11. Jiang Y, Jahagirdar BN, Lee-Reinhardt R, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49;2002.

    Google Scholar 

  12. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34;1999.

    Google Scholar 

  13. Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96:10711–10716;1999.

    Google Scholar 

  14. Lois C, Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci USA 90:2074–2077;1993.

    Google Scholar 

  15. Markakis EA, Gage FH. Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. J Comp Neurol 406:449–460;1999.

    Google Scholar 

  16. McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, Gottlieb DI, Choi DW. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5:1410–1412;1999.

    Google Scholar 

  17. Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, Helwig B, Beerenstrauch M, Abou-Easa K, Hildreth T, Troyer D. Matrix cells from Wharton's jelly form neurons and glia. Stem Cells 21:50–60;2003.

    Google Scholar 

  18. Nguyen L, Rigo JM, Rocher V, Belachew S, Malgrange B, Rogister B, Leprince P, Moonen G. Neurotransmitters as early signals for central nervous system development. Cell Tissue Res 305:187–202;2001.

    Google Scholar 

  19. Ni L, Wen Y, Peng X, Jonakait GM. Antioxidants N-acetylcysteine (NAC) and 2-mercaptoethanol (2-ME) affect the survival and differentiative potential of cholinergic precursors from the embryonic septal nuclei and basal forebrain: Involvement of ras signaling. Brain Res Dev Brain Res 130:207–216;2001.

    Google Scholar 

  20. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256;2000.

    Google Scholar 

  21. Sanchez-Ramos JR, Song S, Kamath SG, Zigova T, Willing A, Cardozo-Pelaez F, Stedeford T, Chopp M, Sanberg PR. Expression of neural markers in human umbilical cord blood. Exp Neurol 171:109–115;2001.

    Google Scholar 

  22. Sarnat HB, Nochlin D, Born DE. Neuronal nuclear antigen (NeuN): A marker of neuronal maturation in early human fetal nervous system. Brain Dev 20:88–94;1998.

    Google Scholar 

  23. Schinstine M, Iacovitti L. 5-Azacytidine and BDNF enhance the maturation of neurons derived from EGF-generated neural stem cells. Exp Neurol 144:315–325;1997.

    Google Scholar 

  24. Solbach S, Celio MR. Ontogeny of the calcium binding protein parvalbumin in the rat nervous system. Anat Embryol (Berl) 184:103–124;1991.

    Google Scholar 

  25. Strubing C, Ahnert-Hilger G, Shan J, Wiedenmann B, Hescheler J, Wobus AM. Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mech Dev 53:275–287;1995.

    Google Scholar 

  26. Stull ND, Jung JW, Iacovitti L. Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins. Brain Res Dev Brain Res 130:91–98;2001.

    Google Scholar 

  27. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416:542–545;2002.

    Google Scholar 

  28. White K, Bruckner JV, Guess WL. Toxicological studies of 2-mercaptoethanol. J Pharm Sci 62:237–241;1973.

    Google Scholar 

  29. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370;2000.

    Google Scholar 

  30. Ying QL, Nichols J, Evans EP, Smith AG. Changing potency by spontaneous fusion. Nature 416:545–548;2002.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei

    Yu-Tsung Shih & Yun-Chih Cheng

  2. Department of Physiology, Chinese Medical College, Taichung, Taiwan, ROC

    Ming-Yuan Min

  3. Department of Anatomy, School of Medicine, National Yang-Ming University, No. 155 Sec. 2, Li-Nung Street, 112, Taipei, Taiwan (ROC)

    Yu-Show Fu

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  1. Yu-Show Fu
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Fu, YS., Shih, YT., Cheng, YC. et al. Transformation of human umbilical mesenchymal cells into neurons in vitro. J Biomed Sci 11, 652–660 (2004). https://doi.org/10.1007/BF02256131

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  • DOI: https://doi.org/10.1007/BF02256131

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