title: Bone marrow-derived cells migrate to line the vessels of the CNS: opportunities for gene delivery to CNS vasculature.
abstract: Using bone marrow (BM)-directed gene transfer and permanent transduction via recombinant SV40-derived vectors, we previously reported that BM-derived cells may be progenitors of CNS cells, such as neurons in normal adult animals. In this study, we asked whether the same was true for the CNS blood vessels, that is, whether marrow-resident precursors can migrate to the vasculature of the CNS. SV40-derived gene delivery vectors, carrying marker epitopes (FLAG or AU1), appended to carrier proteins, were injected directly into the femoral BM of rats or rabbits. Controls received intramarrow SV(BUGT), a control vector. Transgene expression was then examined in the vasculature. Endothelial cells expressing the transgenes were observed in the vessels of the striatum, principally localized in laminin- or CD31-positive structures (markers of brain blood vessels). Results in both animal models and with both transgenes were similar. Thus, under physiologic conditions and in the absence of CNS or vascular injury, BM-derived cells can migrate to, and form an endothelial lining for, brain blood vessels. Intramarrow gene delivery may provide an avenue to deliver genes to the vascular endothelium of the CNS.
authors: Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jplouboutin@hotmail.com
authors: J-P
authors: JP
authors: Louboutin
authors: A A
authors: AA
authors: Chekmasova
authors: B A S
authors: BA
authors: Reyes
authors: E J
authors: EJ
authors: Van Bockstaele
authors: D S
authors: DS
authors: Strayer
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology*; D001921:Brain / Q000098:blood supply*; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013539:Simian virus 40 / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D014161:Transduction, Genetic; D019076:Transgenes