Participation of bone marrow-derived cells in long-term repair processes after experimental stroke.
Bone marrow-derived cells participate in remodeling processes of many ischemia-associated diseases, which has raised hopes for the use of bone marrow as a source for cell-based therapeutic approaches. To study the participation of bone marrow-derived cells in a stroke model, bone marrow from C57BL/6-TgN(ACTbEGFP)1Osb mice that express green fluorescent protein (GFP) in all cells was transplanted into C57BL/6J mice. The recipient mice underwent permanent occlusion of the middle cerebral artery, and bone marrow-derived cells were tracked by fluorescence. The authors investigated the involvement of bone marrow-derived cells in repair processes 6 weeks and 6 months after infarction. Six weeks after occlusion of the artery, more than 90% of the GFP-positive cells in the infarct border zone were microglial cells. Very few GFP-positive cells expressed endothelial markers in the infarct/infarct border zone, and no bone marrow-derived cells transdifferentiated into astrocytes, neurons, or oligodendroglial cells at all time points investigated. The results indicate the need for additional experimental studies to determine whether therapeutic application of nonselected bone marrow will replenish brain cells beyond an increase in microglial engraftment.
Beck
Heike
H
GSF-Research Center for Environment & Health, Institute for Clinical Molecular Biology and Tumor Genetics, Munich, Germany. Heike.Beck@gsf.de
Voswinckel
Robert
R
Wagner
Shawn
S
Ziegelhoeffer
Tibor
T
Heil
Matthias
M
Helisch
Armin
A
Schaper
Wolfgang
W
Acker
Till
T
Hatzopoulos
Antonis K
AK
Plate
Karl H
KH
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis; D000367:Age Factors; D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002831:Choroid Plexus / Q000737:chemistry / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000032:analysis; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy*; D037102:Lectins / Q000032:analysis; D008164:Luminescent Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000737:chemistry / Q000166:cytology*; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D007202:Indicators and Reagents; D037102:Lectins; D008164:Luminescent Proteins; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases