Migration and differentiation of human mesenchymal stem cells in the normal rat brain.
OBJECTIVE
Transplanted mesenchymal stem cells migrate toward brain lesions and differentiate into neurons, glial cells, and neural stem cells in diseased or injured animal models. The migratory routes and differentiation patterns of mesenchymal stem cells in normal rats are, however, unknown. Here, labelled human mesenchymal stem cells (or saline) were transplanted into the striatum of adult rats to observe their migration and differentiation.


METHODS
Labelled human mesenchymal stem cells were transplanted into the right striatum of adults rats (n = 24). Brain sections were examined for migratory routes of labelled human mesenchymal stem cells by immunohistochemistry method, fluorescence microscope and laser scanning confocal microscopy observation, and Prussian blue staining. Moreover, the differentiation of human mesenchymal stem cells was detected by double immunohistochemistry.


RESULTS
After 3 days, most human mesenchymal stem cells resided around the injection sites. Human mesenchymal stem cells were found in or around the corpus callosum and the subependymal layer after 7 days. A great number of human mesenchymal stem cells were detected throughout the brain on both ipsilateral and contralateral sides after 14 days. A high concentration of donor cells persisted in the corpus callosum, the external capsule and the subventricular zone. In addition, the incorporated human mesenchymal stem cells were neuronal nuclei- and glial fibrillary acidic protein-positive.


CONCLUSIONS
Human mesenchymal stem cells migrate throughout the brain mainly along with the axis of corpus callosum external capsule and the subependymal layer, and differentiate into neurons and astrocytes rather than neural stem cells.
Li
Jia-Mei
JM
Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
Zhu
Hua
H
Lu
Shan
S
Liu
Ying
Y
Li
Qin
Q
Ravenscroft
Paula
P
Xu
Yan-Feng
YF
Huang
Lan
L
Ma
Chun-Mei
CM
Bezard
Erwan
E
Zhao
Robert Chun-Hua
RC
Wang
Ren-Zhi
RZ
Qin
Chuan
C
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D003342:Corpus Striatum / Q000601:surgery; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009414:Nerve Growth Factors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D009414:Nerve Growth Factors