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TISSUE-SPECIFIC STEM CELLS

Rat Bone Marrow Progenitor Cells Transduced In Situ by rSV40 Vectors Differentiate into Multiple Central Nervous System Cell Lineages

^aDepartment of Pathology, Anatomy, and Cell Biology and
^bDepartment of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Key Words. Stem cells • Bone marrow • Gene transfer • SV40 • Brain • Hippocampus

Correspondence: Jean-Pierre Louboutin, M.D., Ph.D., Department of Pathology, Anatomy, and Cell Biology, Room 255, Jefferson Medical College, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA. Telephone: 215-503-1268; Fax: 215-503-1156; e-mail: jplouboutin{at}hotmail.com

Received March 3, 2006; accepted for publication August 8, 2006.
First published online in STEM CELLS EXPRESS   September 7, 2006.



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.