Secretome of Mesenchymal Progenitors from the Umbilical Cord Acts as Modulator of Neural/Glial Proliferation and Differentiation
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It was recently shown that the conditioned media (CM) of Human Umbilical Cord Perivascular Cells (HUCPVCs), a mesenchymal progenitor population residing within the Wharton Jelly of the umbilical cord, was able to modulate in vitro the survival and viability of different neuronal and glial cells populations. In the present work, we aimed to assess if the secretome of HUCPVCs is able to 1) induce the differentiation of human telencephalon neural precursor cells (htNPCs) in vitro, and 2) modulate neural/glial proliferation, differentiation and survival in the dentate gyrus (DG) of adult rat hippocampus. For this purpose, two separate experimental setups were performed: 1) htNPCs were incubated with HUCPVCs-CM for 5 days after which neuronal differentiation was assessed and, 2) HUCPVCs, or their respective CM, were injected into the DG of young adult rats and their effects assessed 7 days later. Results revealed that the secretome of HUCPVCs was able to increase neuronal cell differentiation in vitro; indeed, higher densities of immature (DCX+ cells) and mature neurons (MAP-2+ cells) were observed when htNPCs were incubated with the HUCPVCs-CM. Additionally, when HUCPVCs and their CM were injected in the DG, results revealed that both cells or CM were able to increase the endogenous proliferation (BrdU+ cells) 7 days after injection. It was also possible to observe an increased number of newborn neurons (DCX+ cells), upon injection of HUCPVCs or their respective CM. Finally western blot analysis revealed that after CM or HUCPVCs transplantation, there was an increase of fibroblast growth factor-2 (FGF-2) and, to a lesser extent, of nerve growth factor (NGF) in the DG tissue. Concluding, our results have shown that the transplantation of HUCPVCs or the administration of their secretome were able to potentiate neuronal survival and differentiation in vitro and in vivo.
KeywordsCNS Neurogenesis MSCs HUCPVCs Secretome
Foundation Calouste Gulbenkian for funds under the scope of the Gulbenkian Programme to Support Cutting Edge Research in Life Sciences; Portuguese Foundation for Science and Technology (FCT) for Ciência 2007 program and IF Development Grant (A.J. Salgado), and pre-doctoral fellowship to F.G. Teixeira (SFRH / BD / 69637 / 2010); John E. Davies for kindly providing the HUCPVCs used in this work.
Conflict of Interest
The author(s) declare that they have no competing interests.
- 16.Cristofanilli, M., Harris, V. K., Zigelbaum, A., Goossens, A. M., Lu, A., Rosenthal, H., et al. (2011). Mesenchymal stem cells enhance the engraftment and myelinating ability of allogeneic oligodendrocyte progenitors in dysmyelinated mice. Stem Cells and Development, 20(12), 2065–76.CrossRefPubMedGoogle Scholar
- 17.Cova, L., Armentero, M. T., Zennaro, E., Calzarossa, C., Bossolasco, P., Busca, G., et al. (2010). Multiple neurogenic and neurorescue effects of human mesenchymal stem cell after transplantation in an experimental model of Parkinson’s disease. Brain Research, 1311, 12–27.CrossRefPubMedGoogle Scholar
- 23.Salgado, A. J., Fraga, J. S., Mesquita, A. R., Neves, N. M., Reis, R. L., & Sousa, N. (2010). Role of human umbilical cord mesenchymal progenitors conditioned media in neuronal/glial cell densities, viability, and proliferation. Stem Cells and Development, 19(7), 1067–74.CrossRefPubMedGoogle Scholar
- 32.Carvalho, M. M., Teixeira, F. G., Reis, R. L., Sousa, N., & Salgado, A. J. (2011). Mesenchymal stem cells in the umbilical cord: phenotypic characterization, secretome and applications in central nervous system regenerative medicine. Current Stem Cell Research & Therapy, 6(3), 221–8.CrossRefGoogle Scholar
- 33.Ribeiro, C. A., Fraga, J. S., Graos, M., Neves, N. M., Reis, R. L., Gimble, J. M., et al. (2012). The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations. Stem Cell Research & Therapy, 3(3), 18.CrossRefGoogle Scholar
- 36.Ding, D. C., Shyu, W. C., Chiang, M. F., Lin, S. Z., Chang, Y. C., Wang, H. J., et al. (2007). Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiology of Disease, 27(3), 339–53.CrossRefPubMedGoogle Scholar
- 39.Mendez, I., Dagher, A., Hong, M., Gaudet, P., Weerasinghe, S., McAlister, V., et al. (2002). Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases. Journal of Neurosurgery, 96(3), 589–96.CrossRefPubMedGoogle Scholar
- 40.Mendez, I., Sanchez-Pernaute, R., Cooper, O., Vinuela, A., Ferrari, D., Bjorklund, L., et al. (2005). Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain, 128(Pt 7), 1498–510.CrossRefPubMedCentralPubMedGoogle Scholar
- 41.Paxinos, G., & Watson, C. (2004). Rat brain in stereotaxic coordinates (5th ed.). San Diego: Academic.Google Scholar
- 44.Baer, P.C. and Geiger, H. (2012). Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells International, p. 812693.Google Scholar
- 48.Ribeiro, C. A., Salgado, A. J., Fraga, J. S., Silva, N. A., Reis, R. L., & Sousa, N. (2011). The secretome of bone marrow mesenchymal stem cells-conditioned media varies with time and drives a distinct effect on mature neurons and glial cells (primary cultures). Journal of Tissue Engineering and Regenerative Medicine, 5(8), 668–72.CrossRefPubMedGoogle Scholar
- 49.Munoz, J. R., Stoutenger, B. R., Robinson, A. P., Spees, J. L., & Prockop, D. J. (2005). Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proceedings of the National Academy of Sciences of the United States of America, 102(50), 18171–6.CrossRefPubMedCentralPubMedGoogle Scholar
- 54.Chen, J., Lee, C. T., Errico, S. L., Becker, K. G., & Freed, W. J. (2007). Increases in expression of 14-3-3 eta and 14-3-3 zeta transcripts during neuroprotection induced by delta9-tetrahydrocannabinol in AF5 cells. Journal of Neuroscience Research, 85(8), 1724–33.CrossRefPubMedCentralPubMedGoogle Scholar
- 55.Bonner, H. P., Concannon, C. G., Bonner, C., Woods, I., Ward, M. W., & Prehn, J. H. (2010). Differential expression patterns of Puma and Hsp70 following proteasomal stress in the hippocampus are key determinants of neuronal vulnerability. Journal of Neurochemistry, 114(2), 606–16.CrossRefPubMedGoogle Scholar