Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury.
To test the efficacy of various delivery routes of stem cells to treat cerebral injury, we investigated the parenchymal distribution of marrow stromal cells (MSCs) injected into the internal carotid artery (ICA) of the adult rat after traumatic brain injury (TBI). Bromodeoxyuridine (BrdU)-labeled MSCs were injected via the ipsilateral ICA at 24 h after TBI. Using histology and immunohistochemistry, the distribution of implanted MSCs was analyzed at 7 days after transplantation. Four groups (n = 4/group) were studied: group 1, animals transplanted with MSCs cultured with NGF and BDNF at 24 h after TBI; group 2, animals transplanted with MSCs cultured without NGF and BDNF; group 3, animals injected with a placebo, phosphate buffered saline into the ICA at 24 h after TBI; and group 4, rats subjected to TBI only. In groups 1 and 2, BrdU-positive cells were localized to the boundary zone of the lesion, corpus callosum and cortex of the ipsilateral hemisphere. The number of BrdU-positive cells was significantly higher in the ipsilateral hemisphere than in the contralateral hemisphere. More MSCs infused intraarterially engrafted in group 1 (18.9%) than in group 2 (14.4%, p < 0.05). Using double staining, BrdU-positive cells expressed MAP-2, NeuN, and GFAP in both groups 1 and 2, with this expression being greater in group 1 and the difference between two groups reaching statistical significance in case of MAP-2. Our data suggest that intraarterial transplantation of MSCs is a viable route for the intracerebral administration of MSCs for the treatment of TBI, since MSCs infused intraarterially after TBI survive and migrate into the brain. Some implanted MSCs express proteins specific to neurons and astrocytes. The addition of NGF and BDNF promote migration of MSCs into the brain and subsequent expression of neuronal protein MAP-2.
Lu
D
D
Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
Li
Y
Y
Wang
L
L
Chen
J
J
Mahmood
A
A
Chopp
M
M
D000818:Animals; D000963:Antimetabolites; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D001921:Brain / Q000166:cytology; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy*; D001973:Bromodeoxyuridine; D002452:Cell Count; D002465:Cell Movement; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007269:Injections, Intra-Arterial; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*
D000963:Antimetabolites; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D001973:Bromodeoxyuridine