Rat bone marrow progenitor cells transduced in situ by rSV40 vectors differentiate into multiple central nervous system cell lineages.
Using bone marrow-directed gene transfer, we tested whether bone marrow-derived cells may function as progenitors of central nervous system (CNS) cells in adult animals. SV40-derived gene delivery vectors were injected directly into femoral bone marrow, and we examined transgene expression in blood and brain for 0-16 months thereafter by immunostaining for FLAG epitope marker. An average of 5% of peripheral blood cells and 25% of femoral marrow cells were FLAG(+) throughout the study. CNS FLAG-expressing cells were mainly detected in the dentate gyrus (DG) and periventricular subependymal zone (PSZ). Although absent before 1 month and rare at 4 months, DG and PSZ FLAG(+) cells were abundant 16 months after bone marrow injection. Approximately 5% of DG cells expressed FLAG, including neurons (48.6%) and microglia (49.7%), and occasional astrocytes (1.6%), as determined by double immunostaining for FLAG and lineage markers. These data suggest that one or more populations of cells resident within adult bone marrow can migrate to the brain and differentiate into CNS-specific cells.
Louboutin
Jean-Pierre
JP
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA. jplouboutin@hotmail.com
Liu
Bianling
B
Reyes
Beverly A S
BA
Van Bockstaele
Elisabeth J
EJ
Strayer
David S
DS
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002490:Central Nervous System / Q000166:cytology*; D004274:DNA, Recombinant / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology; D004805:Ependyma / Q000166:cytology; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000378:metabolism; D017628:Microglia / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009842:Oligopeptides; D010455:Peptides; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013539:Simian virus 40 / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes
D004274:DNA, Recombinant; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; C085706:FLAG peptide