Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia.
The present study examined the effects of human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 x 10(6) HUCB-derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate-buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB-derived MSCs expressed neuroprotective factors, such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB-derived MSCs could be useful in clinical treatment of cerebral ischemia.
Chung
Dai-Jung
DJ
Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
Choi
Chi-Bong
CB
Lee
Sung-Ho
SH
Kang
Eun-Hee
EH
Lee
Jae-Hoon
JH
Hwang
Soo-Han
SH
Han
Hoon
H
Lee
Jong-Hwan
JH
Choe
Bo-Young
BY
Lee
Soo-Yeol
SY
Kim
Hwi-Yool
HY
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D036101:Cord Blood Stem Cell Transplantation; D004285:Dogs; D005455:Fluorescent Antibody Technique; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020127:Recovery of Function; D018709:Statistics, Nonparametric; D013997:Time Factors; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor