Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain.
A distinct population of white matter progenitor cells (WMPCs), competent but not committed to generate oligodendrocytes, remains ubiquitous in the adult human subcortical white matter. These cells are present in both sexes and into senescence and may constitute as much as 4% of the cells of adult human capsular white matter. Transduction of adult human white matter dissociates with plasmids bearing early oligodendrocytic promoters driving fluorescent reporters permits the separation of these cells at high yield and purity, as does separation based on their expression of A2B5 immunoreactivity. Isolates of these cells survive xenograft to lysolecithin-demyelinated brain and migrate rapidly to infiltrate these lesions, without extending into normal white matter. Within several weeks, implanted progenitors mature as oligodendrocytes, and develop myelin-associated antigens. Lentiviral tagging with green fluorescent protein confirmed that A2B5-sorted progenitors develop myelin basic protein expression within regions of demyelination and that they fail to migrate when implanted into normal brain. Adult human white matter progenitor cells can thus disperse widely through regions of experimental demyelination and are able to differentiate as myelinating oligodendrocytes. This being the case, they may constitute appropriate vectors for cell-based remyelination strategies.
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
Martha S
MS
Windrem
Neeta S
NS
Roy
Jeremy
J
Wang
Marta
M
Nunes
Abdellatif
A
Benraiss
Robert
R
Goodman
Guy M
GM
McKhann
Steven A
SA
Goldman
D000328:Adult; D000367:Age Factors; D000818:Animals; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D003711:Demyelinating Diseases / Q000601:surgery*; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D006801:Humans; D018189:Immunomagnetic Separation; D007202:Indicators and Reagents / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008244:Lysophosphatidylcholines; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000032:analysis; D009186:Myelin Sheath; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000737:chemistry / Q000166:cytology*; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014183:Transplantation, Heterologous
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D049452:Green Fluorescent Proteins