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Functional recovery after transplantation of mouse bone marrow-derived mesenchymal stem cells for hypoxic-ischemic brain injury in immature rats

Korean Journal of Pediatrics 2009;52(7):824-831.
Published online July 15, 2009.
Functional recovery after transplantation of mouse bone marrow-derived mesenchymal stem cells for hypoxic-ischemic brain injury in immature rats
Wooksun Choi, Hye Kyung Shin, So-Hee Eun, Hoon Chul Kang, Sung Won Park, Kee Hwan Yoo, Young Sook Hong, Joo Won Lee, Baik-Lin Eun
Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
저산소 허혈 뇌 손상을 유발시킨 미성숙 흰쥐에서 마우스 골수 기원 중간엽 줄기 세포 이식 후 기능 회복
최욱선, 신혜경, 은소희, 강훈철, 박성원, 유기환, 홍영숙, 이주원, 은백린
고려대학교 의과대학 소아과학교실
Correspondence: 
Baik-Lin Eun, Email: bleun@chollian.net, bleun@korea.ac.kr
Abstract
Purpose
: We aimed to investigate the efficacy of and functional recovery after intracerebral transplantation of different doses of mouse mesenchymal stem cells (mMSCs) in immature rat brain with hypoxic-ischemic encephalopathy (HIE).
Methods
: Postnatal 7-days-old Sprague-Dawley rats, which had undergone unilateral HI operation, were given stereotaxic intracerebral injections of either vehicle or mMSCs and then tested for locomotory activity in the 2nd, 4th, 6th, and 8th week of the stem cell injection. In the 8th week, Morris water maze test was performed to evaluate the learning and memory dysfunction for a week.
Results
: In the open field test, no differences were observed in the total distance/the total duration (F=0.412, P=0.745) among the 4 study groups. In the invisible-platform Morris water maze test, significant differences were observed in escape latency (F=380.319, P<0.01) among the 4 groups. The escape latency in the control group significantly differed from that in the high-dose mMSC and/or sham group on training days 2-5 (Scheffe's test, P<0.05) and became prominent with time progression (F=6.034, P<0.01). In spatial probe trial and visible-platform Morris water maze test, no significant improvement was observed in the rats that had undergone transplantation.
Conclusion
: Although the rats that received a high dose of mMSCs showed significant recovery in the learning-related behavioral test only, our data support that mMSCs may be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal dose that shows maximal efficacy for HIE treatment.
Key Words: Cerebral ischemia, Mesenchymal stem cell, Newborn


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