Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells.
Human bone marrow stromal cells (hMSCs) enhance neurological recovery after stroke in rodents, possibly via induction of growth factors. We therefore elected to test the effects of hMSC treatment on insulin-like growth factor 1 (IGF-1), which plays an important role in growth, development, neuroprotection and repair in the adult. Rats (n=57) were subjected to permanent middle cerebral artery occlusion (MCAo) and injected intravenously with 3 x 10(6) hMSCs or phosphate-buffered saline (PBS) at 1 day after MCAo. Functional outcome was measured after MCAo using a modified Neurological Severity Score (mNSS). Gene expression of IGF-1 and IGF-1 receptor (IGF-1R) in the ischemic brain tissue were measured at 2 and 7 days after MCAo using reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to measure the expression of bromodeoxyuridine (BrdU), doublecortin (DCX), IGF-1 and IGF-1R at 7, 14 and 30 days after MCAo. Treatment of MCAo with hMSCs significantly improved functional recovery from 14 to 30 days. MAB1281-labeled hMSCs entered the ischemic brain and increased time-dependently. hMSC treatment significantly increased IGF-1 mRNA and BrdU(+), DCX(+), IGF-1(+) and IGF-1R(+) cells compared to PBS-treated rats (p<0.05). The percentage of BrdU(+) or DCX(+) cells colocalized with IGF-1 increased in the hMSC-treated rats compared to the PBS-treated rats (p<0.05). IGF-1 and IGF-1R may contribute to improved functional recovery and increased neurogenesis after treatment of stroke with hMSCs.
Zhang
Jing
J
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Li
Yi
Y
Chen
Jieli
J
Yang
Maozhou
M
Katakowski
Mark
M
Lu
Mei
M
Chopp
Michael
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000628:therapy*; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D000089662:Doublecortin Protein; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D020127:Recovery of Function; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D020521:Stroke / Q000628:therapy; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D014183:Transplantation, Heterologous
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1