Neural Stem Cells for Cns Repair: State of the Art and Future Directions (original) (raw)
Abstract
Approximately 10-15 years ago, we and a small group of other investigators recognized cells with an unanticipated degree of plasticity and multipotency existed in the CNS. These cells are now called neural stem cells (NSCs). They probably represented the cellular basis for a great deal of unrecognized plasticity programmed into the developing and post-developmental CNS. It is likely that therapeutic advantage might be realized by harnessing this plasticity. Two complementary goals drive the motivation to study NSCs both in situ and following their isolation and propagation ex vivo. The first is to understand the processes of commitment, differentiation, migration and plasticity in the mammalian nervous system during development and degeneration. The second is to use such cells for therapeutic purposes (at all ages). The pursuit of one goal typically nurtures the other, and our lab pursues these two overlapping areas of investigation. In fact, our hypothesis has been that, by first understanding the fundamental biology of pluripotent NSCs (whose role is to mediate organogenesis, homeostasis and reconstitution), and then exploiting those novel molecular and/or cellular replacement clinical therapies for some developmental, degenerative and acquired human neurological dysfunctions. In fact, these actual hNSCs may have the potential for direct human application.
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
- E.Y. Snyder, D.L. Deitcher, C. Walsh, S. Arnold-Aldea, E.A. Hartweig, C.L. Cepko, Multipotent neural cell lines can engraft and participate in development of mouse cerebellum, Cell 68:33 (1992).
Article CAS PubMed Google Scholar - V. Ourednik, J. Ourednik, K.I. Park, E.Y. Snyder, Neural stem cells: a versatile tool for cell replacement and gene therapy in the CNS, Clin. Genet. 46: 267 (1999).
Article Google Scholar - E.Y. Snyder, Neural stem-like cells: developmental lessons with therapeutic potential, The Neuroscientist 4: 408 (1998).
Article Google Scholar - J. Wagner, P. Akerud, D. Castro, P.C. Holm, E.Y. Snyder, T. Perlmann, E. Arenas, Type 1 astrocytes induce a midbrain dopaminergic phenotype in Nurrl-overexpressing neural stem cells, Nature Biotech. 17:653 (1999).
Article CAS Google Scholar - C.M. Rosario, B.D. Yandava, B. Kosaras, D. Zurakowski, R.L. Sidman, E.Y. Snyder, Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action, Development 124:4213 (1997).
CAS PubMed Google Scholar - E.Y. Snyder, C.H. Yoon, J.D. Flax, J.D. Macklis, Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex, Proc. Natl. Acad. Sci. USA 94:11663 (1997).
Article CAS PubMed PubMed Central Google Scholar - K.I. Park, S. Liu, J.D. Flax, S. Nissim, P.E. Stieg, E.Y. Snyder, Transplantation of neural progenitor and stem-like cells: developmental insights may suggest new therapies for spinal cord and other CNS dysfunction, J. Neurotrauma 16:675 (1999).
Article CAS PubMed Google Scholar - K.I. Park, E.Y. Snyder, Injury shifts developmental patterns to promote establishment of lost neural cells in “non-neurogenic” CNS regions, Soc. Neurosci. Abstr. (in press).
Google Scholar - E.Y. Snyder, R.M. Taylor, J.H. Wolfe, Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain, Nature 374:367 (1995).
Article CAS PubMed Google Scholar - H.D. Lacorazza, J.D. Flax, E.Y. Snyder, M. Jendoubi, Expression of human G3-hexosaminidase a-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells, Nature Medicine 4:424 (1996).
Article Google Scholar - F.J. Rubio, Z. Kokaia, A. Arco, M.I. Garcia-Simon, E.Y. Snyder, O. Lindvall, J. Satrustegui, A. Martinez-Serrano, BDNF gene transfer to the mammalian brain using CNS-derived neural precursors, Gene Therapy 6: 1851 (1999).
Article CAS PubMed Google Scholar - B.D. Yandava, L.L. Billinghurst, E.Y. Snyder, Global cell replacement is feasible via neural stem cell transplantation: evidence from the shiverer dysmyelinated mouse brain, Proc. Natl. Acad. Sci. USA 96:7029 (1999).
Article CAS PubMed PubMed Central Google Scholar - L.L. Billinghurst, R.M. Taylor, E.Y. Snyder, Remyelination: cellular and gene therapy, Sem. in Ped. Neurol. 5: 211 (1998).
Article CAS Google Scholar - L. Doering, E.Y. Snyder, Cholinergic expression by a neural stem cell line grafted to the adult medial septum/diagonal band complex, J. Neurosci. Res. 61:597 (2000).
Article CAS PubMed Google Scholar - K.S. Aboody, A. Brown, N.G. Rainov, K.A. Bower, S. Liu, W. Yang, J.E. Small, U. Herrlinger, V. Ourednik, P.M. Black, X.O. Breakefield, E.Y. Snyder, Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial tumors, Proc. Natl. Acad. Sci. USA 97:12846 (2000).
Article CAS PubMed PubMed Central Google Scholar - U. Herrlinger, C. Woiciechowski, K.S. Aboody, A.H. Jacobs, N.G. Rainov, E.Y. Snyder, X.O. Breakefield, Neural stem cells for delivery of replication-conditional HSV-1 vectors to intracerebral gliomas, Molecular Therapy 1:347 (2000).
Article CAS PubMed Google Scholar - W.P. Lynch, A.H. Sharpe, E.Y. Snyder, Neural stem cells as engraftable packaging lines can optimize viral vector-mediated gene delivery to the CNS: evidence from studying retroviral env-related neurodegeneration, J. Viral. 73:6841 (1999).
CAS Google Scholar - D.J. Poulsen, C. Favara, E.Y. Snyder, J. Portis, B. Chesebro, Increased neurovirulence of polytropic mouse retroviruses delivered by inoculation of brain with infected neural progenitor cells, Virology 263:23 (1999).
Article CAS PubMed Google Scholar - K.I. Park, E. Lavik, Y.D. Teng, R. Langer, E.Y. Snyder, Transplantation of neural stem cells (NSCs) seeded in biodegradable polyglycolic acid (PGA) scaffolds into hypoxic-ischemic (HI) brain injury, Soc. Neurosci. Abstr. (in press).
Google Scholar - V. Ourednik, J. Ourednik, K.I. Park, Y.D. Teng, K.A. Aboody, K.I. Auguste, R.M. Taylor, B.A. Tate, E.Y. Snyder, Neural stem cells are uniquely suited for cell replacement and gene therapy in the CNS, in Novartis Foundation Symposium: Neural transplantation in neurodegenerative disease: current status and new directions, D.J. Chadwick, J.A. Goode, eds., Wiley & Sons, NY (2000).
Book Google Scholar - J.D. Flax, S. Aurora, C. Yang, C. Simonin, A.M. Wills, L. Billinghurst, M. Jendoubi, R.L. Sidman, J.H. Wolfe, S.U. Kim, E.Y. Snyder, Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes, Nature Biotech. 16:1033 (1998).
Article CAS Google Scholar - A. Villa, E.Y. Snyder, A. Vescovi, A. Martinez-Serrano, Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS, Exp. Neurol. 161:67 (2000).
Article CAS PubMed Google Scholar - A.L. Vescovi, E.Y. Snyder, Establishment and properties of neural stem cell clones: plasticity in vitro and in vivo, Brain Pathology 9:569 (1999).
Article CAS PubMed Google Scholar - E.Y. Snyder, A.L. Vescovi, Stem cells: possibilities or perplexities, Nature Biotech. 18:827 (2000).
Article CAS Google Scholar
Author information
Authors and Affiliations
- Departments of Neurosurgery, Pediatrics, and Neurology Children’s Hospital Harvard Medical School Boston, Massachusetts, USA
Kook In Park, Mahesh Lachyankar, Sahar Nissim & Evan Y. Snyder - Department of Pediatrics, Yongdong Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
Kook In Park
Authors
- Kook In Park
You can also search for this author inPubMed Google Scholar - Mahesh Lachyankar
You can also search for this author inPubMed Google Scholar - Sahar Nissim
You can also search for this author inPubMed Google Scholar - Evan Y. Snyder
You can also search for this author inPubMed Google Scholar
Editor information
Editors and Affiliations
- Schepens Eye Research Institute, Boston, Massachusetts, USA
David A. Sullivan , Darlene A. Dartt & Rose M. Sullivan , & - Harvard Medical School, Boston, Massachusetts, USA
David A. Sullivan & Darlene A. Dartt & - Allergan, Inc., Irvine, California, USA
Michael E. Stern - Tokyo Dental College, Chiba, Japan
Kazuo Tsubota - Ichikawa General Hospital, Chiba, Japan
Kazuo Tsubota - University of New Orleans, New Orleans, Louisiana, USA
B. Britt Bromberg
Rights and permissions
Copyright information
© 2002 Kluwer Academic/Plenum Publishers
About this chapter
Cite this chapter
Park, K.I., Lachyankar, M., Nissim, S., Snyder, E.Y. (2002). Neural Stem Cells for Cns Repair: State of the Art and Future Directions. In: Sullivan, D.A., Stern, M.E., Tsubota, K., Dartt, D.A., Sullivan, R.M., Bromberg, B.B. (eds) Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3. Advances in Experimental Medicine and Biology, vol 506. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0717-8\_188
Download citation
- .RIS
- .ENW
- .BIB
- DOI: https://doi.org/10.1007/978-1-4615-0717-8\_188
- Publisher Name: Springer, Boston, MA
- Print ISBN: 978-1-4613-5208-2
- Online ISBN: 978-1-4615-0717-8
- eBook Packages: Springer Book Archive