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PMID: 8524867 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain.

Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, Peterson DA, Suhr ST, Ray J

Abstract

The dentate gyrus of the hippocampus is one of the few areas of the adult brain that undergoes neurogenesis. In the present study, cells capable of proliferation and neurogenesis were isolated and cultured from the adult rat hippocampus. In defined medium containing basic fibroblast growth factor (FGF-2), cells can survive, proliferate, and express neuronal and glial markers. Cells have been maintained in culture for 1 year through multiple passages. These cultured adult cells were labeled in vitro with bromodeoxyuridine and adenovirus expressing beta-galactosidase and were transplanted to the adult rat hippocampus. Surviving cells were evident through 3 months postimplantation with no evidence of tumor formation. Within 2 months postgrafting, labeled cells were found in the dentate gyrus, where they differentiated into neurons only in the intact region of the granule cell layer. Our results indicate that FGF-2 responsive progenitors can be isolated from the adult hippocampus and that these cells retain the capacity to generate mature neurons when grafted into the adult rat brain.

MeSH Terms
Animals Biomarkers Brain Tissue Transplantation Cell Differentiation Cell Survival Culture Techniques/methods Female Fibroblast Growth Factor 2/pharmacology Fluorescent Antibody Technique Hippocampus/cytology,surgery Neurons/drug effects,transplantation,ultrastructure Rats Rats, Inbred F344 Stem Cell Transplantation Stem Cells/drug effects,ultrastructure
Chemicals
Biomarkers Fibroblast Growth Factor 2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Gage F H
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Coates P W
Palmer T D
Kuhn H G
Fisher L J
Suhonen J O
Peterson D A
Suhr S T
Ray J
References (28)
28 references, click to expand
  1. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats.
    J Comp Neurol. 1965 Jun;124(3):319-35 PMID: 5861717
  2. Perforant path damage results in progressive neuronal death and somal atrophy in layer II of entorhinal cortex and functional impairment with increasing postdamage age.
    J Neurosci. 1994 Nov;14(11 Pt 2):6872-85 PMID: 7965084
  3. Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life.
    Science. 1982 May 21;216(4548):890-2 PMID: 7079742
  4. Changes in the total number of dentate granule cells in juvenile and adult rats: a correlated volumetric and 3H-thymidine autoradiographic study.
    Exp Brain Res. 1982;46(3):315-23 PMID: 7095040
  5. Neuronal proliferation in the 9-month-old rodent-radioautographic study of granule cells in the hippocampus.
    Exp Brain Res. 1983;52(1):1-5 PMID: 6628589
  6. Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus.
    J Neurosci. 1984 Jun;4(6):1429-41 PMID: 6726341
  7. The unbiased estimation of number and sizes of arbitrary particles using the disector.
    J Microsc. 1984 May;134(Pt 2):127-36 PMID: 6737468
  8. On the number of neurons in the dentate gyrus of the rat.
    Brain Res. 1985 Jul 8;338(1):144-50 PMID: 3896391
  9. Brain basic fibroblast growth factor stimulates the proliferation of rat neuronal precursor cells in vitro.
    FEBS Lett. 1987 Jun 8;217(1):1-5 PMID: 3595842
  10. Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections.
    Exp Brain Res. 1988;72(2):399-406 PMID: 2465172
  11. Selective lesions of granule cells by fluid injections into the dentate gyrus.
    Exp Neurol. 1989 Dec;106(3):275-82 PMID: 2480247
  12. Fibroblast growth factor stimulates the proliferation and differentiation of neural precursor cells in vitro.
    J Neurosci Res. 1990 Apr;25(4):463-75 PMID: 2112611
  13. Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain.
    Cell. 1991 Aug 23;66(4):713-29 PMID: 1878969
  14. Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography.
    J Neurosci. 1991 Nov;11(11):3556-64 PMID: 1719164
  15. Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain.
    J Neurosci. 1992 Jan;12(1):249-56 PMID: 1729437
  16. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum.
    Cell. 1992 Jan 10;68(1):33-51 PMID: 1732063
  17. Establishment of pure neuronal cultures from fetal rat spinal cord and proliferation of the neuronal precursor cells in the presence of fibroblast growth factor.
    J Neurosci Res. 1991 Aug;29(4):499-509 PMID: 1724269
  18. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.
    Science. 1992 Mar 27;255(5052):1707-10 PMID: 1553558
  19. De novo generation of neuronal cells from the adult mouse brain.
    Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8591-5 PMID: 1528866
  20. NeuN, a neuronal specific nuclear protein in vertebrates.
    Development. 1992 Sep;116(1):201-11 PMID: 1483388
  21. Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain.
    Neuron. 1993 Feb;10(2):201-12 PMID: 8439409
  22. Proliferation, differentiation, and long-term culture of primary hippocampal neurons.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3602-6 PMID: 8475109
  23. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone.
    Neuron. 1993 Jul;11(1):173-89 PMID: 8338665
  24. Variable morphological differentiation of a raphé-derived neuronal cell line following transplantation into the adult rat CNS.
    Exp Neurol. 1993 Jul;122(1):130-42 PMID: 8339783
  25. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat.
    Neuroscience. 1993 Sep;56(2):337-44 PMID: 8247264
  26. Long-distance neuronal migration in the adult mammalian brain.
    Science. 1994 May 20;264(5162):1145-8 PMID: 8178174
  27. Spinal cord neuroblasts proliferate in response to basic fibroblast growth factor.
    J Neurosci. 1994 Jun;14(6):3548-64 PMID: 8207471
  28. Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs.
    Science. 1977 Sep 9;197(4308):1092-4 PMID: 887941
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1995-12-05
Pages
11879-83
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40506
Subset
IM
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