Derivation and large-scale expansion of multipotent astroglial neural progenitors from adult human brain.
The isolation and expansion of human neural cell types has become increasingly relevant in restorative neurobiology. Although embryonic and fetal tissue are frequently envisaged as providing sufficiently primordial cells for such applications, the developmental plasticity of endogenous adult neural cells remains largely unclear. To examine the developmental potential of adult human brain cells, we applied conditions favoring the growth of neural stem cells to multiple cortical regions, resulting in the identification and selection of a population of adult human neural progenitors (AHNPs). These nestin(+) progenitors may be derived from multiple forebrain regions, are maintainable in adherent conditions, co-express multiple glial and immature markers, and are highly expandable, allowing a single progenitor to theoretically form sufficient cells for approximately 4x10(7) adult brains. AHNPs longitudinally maintain the ability to generate both glial and neuronal cell types in vivo and in vitro, and are amenable to genetic modification and transplantation. These findings suggest an unprecedented degree of inducible plasticity is retained by cells of the adult central nervous system.
Walton
Noah M
NM
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Sutter
Benjamin M
BM
Chen
Huan-Xin
HX
Chang
Lung-Ji
LJ
Roper
Steven N
SN
Scheffler
Bjorn
B
Steindler
Dennis A
DA
D000293:Adolescent; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis; D007621:Karyotyping; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin