Mesenchymal stem-cell transplantation for hypoxic-ischemic brain injury in neonatal rat model.
Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia (HI)] or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20, 30, and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE.
Lee
Jin A
JA
Departments of Pediatrics, Seoul National University Boramae Hospital and Seoul National University College of Medicine, Seoul, South Korea.
Kim
Beyong Il
BI
Jo
Chris Hyunchul
CH
Choi
Chang Won
CW
Kim
Ee-Kyung
EK
Kim
Han-Suk
HS
Yoon
Kang-Sup
KS
Choi
Jung-Hwan
JH
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D033581:Stem Cell Transplantation