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Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

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References

  1. M. A. Aleksandrova, O. V. Podgornyi, M. V. Marei, R. A. Poltavtseva, E. B. Tsitrin, D. V. Gulyaev, L. V. Cherkasova, A. V. Revishchin, L. I. Korochkin, N. G. Khrushchov, and G. N. Sukhikh, Characteristics of human neural stem cells in vitro and after transplantation into rat brain. Bull. Exp. Biol. Med., 139, No. 1, 114-120 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. E. V. Maksimova, Cerebral Cortex Ontogeny [in Russian] Moscow (1990).

  3. O. V. Podgornyi, R. A. Poltavtseva, M. V. Marei, G. T. Sukhikh, and M. A. Aleksandrova, Formation of Neuroepithelial Structures in Culture of Neural Stem Cells from Human Brain. Bull. Exp. Biol. Med., 140, No. 1, 113-117 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. R. A. Poltavtseva, A. V. Revishchin, M. A. Aleksandrova, L. I. Korochkin, I. V. Viktorov, and G. T. Sukhikh, Neural Stem and Progenitor Cells of Human Embryos and Fetuses as a Basis of New Biomedical Technologies. Rus. J. Develop. Biol., 34, No. 3, 171-174 (2003).

    Article  CAS  Google Scholar 

  5. A. Alvarez-Buylla, J. M. García-Verdugo, and A. D. Tramontin, A unified hypothesis on the lineage of neural stem cells. Nat. Rev. Neurosci., 2, No. 4, 287-293 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. P. Barraud, S. Stott, K. Møllgård, M. Parmar, and A. Björklund, In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133. J. Neurosci. Res., 85, No. 2, 250-259 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. J. Baumann, M. Barenys, K. Gassmann, and E. Fritsche, Comparative human and rat “neurosphere assay” for developmental neurotoxicity testing. Curr. Protoc. Toxicol., 59, 12.21.1-12.21.24, doi: 10.1002/0471140856.tx1221s59 (2014).

    Article  Google Scholar 

  8. N. Bayatti, J.A. Moss, L. Sun, P. Ambrose, J. F. Ward, S. Lindsay, and G. J. Clowry, A molecular neuroanatomical study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone. Cereb. Cortex, 18, No. 7, 1536-1548 (2008).

    Article  PubMed  Google Scholar 

  9. T. Ben-Hur, Immunomodulation by neural stem cells. J. Neurol. Sci., 265, Nos. 1-2, 102-104 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. A. Capela and S. Temple, LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1. Dev. Biol., 291, No. 2, 300-313 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. L. P. Deleyrolle and B. A. Reynolds, Isolation, expansion, and differentiation of adult Mammalian neural stem and progenitor cells using the neurosphere assay. Methods Mol. Biol., 549, 91-101 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Y. Fan, G. Marcy, E. S. Lee, S. Rozen, C. N. Mattar, S. N. Waddington, E. L. Goh, M. Choolani, and J. K. Chan, Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming. PLoS One, 9, No. 9, doi: 10.1371/journal.pone.00105985 (2014).

  13. M. Florio, M. Albert, E. Taverna, T. Namba, H. Brandl, E. Lewitus, C. Haffner, A. Sykes, F. K. Wong, J. Peters, E. Guhr, S. Klemroth, K. Prüfer, J. Kelso, R. Naumann, I. Nüsslein, A. Dahl, R. Lachmann, S. Pääbo, and W. B. Huttner, Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science, 347, 1465-1470 (2015).

    Article  CAS  PubMed  Google Scholar 

  14. M. Götz, S. Sirko, J. Beckers, and M. Irmler, Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, in vitro potential, and genome-wide expression analysis. Glia, 63, No. 8, 1452-1468 (2015).

    Article  PubMed  Google Scholar 

  15. Y. L. Gu, L. W. Yin, Z. Zhang, J. Liu, S. J. Liu, L. F. Zhang, and T. H. Wang, Neurotrophin expression in neural stem cells grafted acutely to transected spinal cord of adult rats linked to functional improvement. Cell. Mol. Neurobiol., 32, No. 7, 1089-1097 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. H. Guerrero-Cázares, O. Gonzalez-Perez, M. Soriano-Navarro, G. Zamora-Berridi, J. M. García-Verdugo, and A. Quinoñes-Hinojosa, Cytoarchitecture of the lateral ganglionic eminence and rostral extension of the lateral ventricle in the human fetal brain. J. Comp. Neurol., 519, No. 6, 1165-1180 (2011).

    Article  PubMed  Google Scholar 

  17. D. V. Hansen, J. H. Lui, P. R. Parker, and A. R. Kriegstein, Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature, 464, 554-561 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. T. Imura, I. Nakano, H. I. Kornblum, and M. V. Sofroniew, Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes. Glia, 53, No. 3, 277-293 (2006).

    Article  PubMed  Google Scholar 

  19. N. Kamei, N. Tanaka, Y. Oishi, T. Hamasaki, K. Nakanishi, N. Sakai, and M. Ochi, BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote corticospinal axon growth in organotypic cocultures. Spine (Phila Pa 1976), 32, No. 12, 1272-1278 (2007).

    Article  Google Scholar 

  20. H. J. Kim, E. McMillan, F. Han, and C. N. Svendsen, Regionally specified human neural progenitor cells derived from the mesencephalon and forebrain undergo increased neurogenesis following overexpression of ASCL1. Stem Cells, 27, No. 2, 390-398 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. V. R. King, A. McBride, and J. V. Priestley, Immunohistochemical expression of the alpha5 integrin subunit in the normal adult rat central nervous system. J. Neurocytol., 30, No. 3, 243-252 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. S. A. Louis, C. K. Mak, and B. A. Reynolds, Methods to culture, differentiate, and characterize neural stem cells from the adult and embryonic mouse central nervous system. Methods Mol. Biol., 946, 479-506 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. L. Mazzini, M. Gelati, D. C. Profico, G. Sgaravizzi, M. Projetti Pensi, G. Muzi, C. Ricciolini, L. Rota Nodari, S. Carletti, C. Giorgi, C. Spera, F. Domenico, E. Bersano, F. Petruzzelli, C. Cisari, A. Maglione, M. F. Sarnelli, A. Stecco, G. Querin, S. Masiero, R. Cantello, D. Ferrari, C. Zalfa, E. Binda, A. Visioli, D. Trombetta, A. Novelli, B. Torres, L. Bernardini, A. Carriero, P. Prandi, S. Servo, A. Cerino, V. Cima, A. Gaiani, N. Nasuelli, M. Massara, J. Glass, G. Sorarù, N. M. Boulis, and A. L. Vescovi, Human neural stem cell transplantation in ALS: initial results from a phase I trial. J. Transl. Med., 13, 17, doi: 10.1186/s12967-014-0371-2 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  24. J. A. Miller, S. L. Ding, S. M. Sunkin, K. A. Smith, L. Ng, A. Szafer, A. Ebbert, Z. L. Riley, J. J. Royall, K. Aiona, J. M. Arnold, C. Bennet, D. Bertagnolli, K. Brouner, S. Butler, S. Caldejon, A. Carey, C. Cuhaciyan, R. A. Dalley, N. Dee, T. A. Dolbeare, B. A. Facer, D. Feng, T. P. Fliss, G. Gee, J. Goldy, L. Gourley, B. W. Gregor, G. Gu, R. E. Howard, J. M. Jochim, C. L. Kuan, C. Lau, C. K. Lee, F. Lee, T. A. Lemon, P. Lesnar, B. McMurray, N. Mastan, N. Mosqueda, T. Naluai-Cecchini, N. K. Ngo, J. Nyhus, A. Oldre, E. Olson, J. Parente, P. D. Parker, S. E. Parry, A. Stevens, M. Pletikos, M. Reding, K. Roll, D. Sandman, M. Sarreal, S. Shapouri, N. V. Shapovalova, E. H. Shen, N. Sjoquist, C. R. Slaughterbeck, M. Smith, A. J. Sodt, D. Williams, L. Zöllei, B. Fischl, M. B. Gerstein, D. H. Geschwind, I. A. Glass, M. J. Hawrylycz, R. F. Hevner, H. Huang, A. R. Jones, J. A. Knowles, P. Levitt, J. W. Phillips, N. Sestan, P. Wohnoutka, C. Dang, A. Bernard, J. G. Hohmann, and E. S. Lein, Transcriptional landscape of the prenatal human brain. Nature, 508, 199-206 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Z. Mo, A. R. Moore, R. Filipovic, Y. Ogawa, I. Kazuhiro, S. D. Antic, and N. Zecevic, Human cortical neurons originate from radial glia and neuron-restricted progenitors. J. Neurosci., 27, No. 15, 4132-4145 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. C. Moon, M. Ahn, S. Kim, J. K. Jin, K. B. Sim, H. M. Kim, M. Y. Lee, and T. Shin, Temporal patterns of the embryonic intermediate filaments nestin and vimentin expression in the cerebral cortex of adult rats after cryoinjury. Brain Res., 1028, No. 2, 238-242 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. J. Nelander, S. Grealish, and M. Parmar, Human foetal brain tissue as quality control when developing stem cells towards cell replacement therapy for neurological diseases. Neuroreport, 24, No. 18, 1025-1030 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. A. D. Nelson, M. Suzuki, and C. N. Svendsen, A high concentration of epidermal growth factor increases the growth and survival of neurogenic radial glial cells within human neurosphere cultures. Stem Cells, 26, No. 2, 348-355 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. H. Okano and S. Temple, Cell types to order: temporal specification of CNS stem cells. Curr. Opin. Neurobiol., 19, No. 2, 112-119 (2009).

    Article  CAS  PubMed  Google Scholar 

  30. E. Pastrana, V. Silva-Vargas, and F. Doetsch, Eyes wide open: a critical review of sphere-formation as an assay for stem cells. Cell Stem Cell, 8, No. 5, 486-498 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. R. A. Poltavtseva, M. V. Marey, M. A. Aleksandrova, A. V. Revishchin, L. I. Korochkin, and G. T. Sukhikh, Evaluation of progenitor cell cultures from human embryos for neurotransplantation. Brain Res. Dev. Brain Res., 134, Nos. 1-2, 149-154 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. J. Pruszak, K. C. Sonntag, M. H. Aung, R. Sanchez-Pernaute, and O. Isacson, Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populations. Stem Cells, 25, No. 9, 2257-2268 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  33. B. Ray, N. Chopra, J. M. Long, and D. K. Lahiri, Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research. Mol. Brain, 7, 63, doi: 10.1186/s13041-014-0063-0 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  34. I. H. Smart, C. Dehay, P. Giroud, M. Berland, and H. Kennedy, Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb. Cortex, 12, No. 1, 37-53 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  35. M. Shikanai, K. Nakajima, and T. Kawauchi, N-cadherin regulates radial glial fiber-dependent migration of cortical locomoting neurons. Commun. Integr. Biol., 4, No. 3, 326-330 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  36. S. Wang, D. Chandler-Militello, G. Lu, N. S. Roy, A. Zielke, R. Auvergne, N. Stanwood, D. Geschwind, G. Coppola, S. K. Nicolis, F. J. Sim, and S. A. Goldman, Prospective identification, isolation, and profiling of a telomerase-expressing sub-population of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting. J. Neurosci., 30, No. 44, 14,635-14,648 (2010).

    Article  CAS  Google Scholar 

  37. W. Wu, Q. He, X. Li, X. Zhang, A. Lu, R. Ge, H. Zhen, A. E. Chang, Q. Li, and L. Shen, Long-term cultured human neural stem cells undergo spontaneous transformation to tumor-initiating cells. Int. J. Biol. Sci., 7, No. 6, 892-901 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. X. Yin, L. Li, X. Zhang, Y. Yang, Y. Chai, X. Han, and Z. Feng, Development of neural stem cells at different sites of fetus brain of different gestational age. Int. J. Clin. Exp. Pathol., 6, No. 12, 2757-2764 (2013).

    PubMed  PubMed Central  Google Scholar 

  39. N. Zecevic, Y. Chen, and R. Filipovic, Contributions of cortical subventricular zone to the development of the human cerebral cortex. J. Comp. Neurol., 491, No. 2, 109-122 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  40. R. Zietlow, S. V. Precious, C. M. Kelly, S. B. Dunnett, and A. E. Rosser, Long-term expansion of human foetal neural progenitors leads to reduced graft viability in the neonatal rat brain. Exp. Neurol., 235, No. 2, 563-573 (2012).

    Article  PubMed  Google Scholar 

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Correspondence to R. A. Poltavtseva.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 1, pp. 65-76, January, 2016

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Aleksandrova, M.A., Poltavtseva, R.A., Marei, M.V. et al. Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro . Bull Exp Biol Med 161, 197–208 (2016). https://doi.org/10.1007/s10517-016-3375-5

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  • DOI: https://doi.org/10.1007/s10517-016-3375-5

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