Effect of human embryonic stem cell-derived neuronal precursor cell transplantation into the cerebral infarct model of rat with exercise.
We analyzed the therapeutic effect of the transplantation of the human embryonic stem cell (NIH Code: MB01)-derived neuronal precursor (hES-NP) cell and post-ischemic exercise in rats with the middle cerebral artery (MCA) infarct model. A cortical infarct was induced in 20 adult Sprague-Dawley rats by occlusion and reperfusion of the MCA. The rats were divided into four groups: hES-NP cell transplantation and exercise, transplantation only, exercise only, and Sham-operated with no exercise. In the cell-transplanted group, hES-NP cells were transplanted by stereotactic inoculation into the ipsilateral basal ganglia 7 days after infarct. We evaluated the clinical recovery of deficit, the size of infarct and the survival, migration, and differentiation of the transplanted cells. The transplanted hES-NP cells survived robustly in the ischemic brains 3 weeks post transplant. The majority of migrating cells in the ischemic rats had a neuronal phenotype. The clinical scores of all of the experimental groups were better than those of the Sham-operated group. Whereas the exercise-only group showed continuous clinical improvement, the cell-transplanted groups manifested less improvement than the exercise-only group. Moreover, the cell-transplanted groups did not differ in clinical improvement according to postinfarct-exercise or not. The infarct size was significantly reduced in both the cell-transplanted groups and the post-ischemic exercise group, compared with the Sham-operated group; however, the reduction of infarct size was most prominent in the exercise-only group. In our study, the inoculated site of the basal ganglia showed some damage induced by inoculation, such as loss of neuroglial cells, reactive gliosis and microcalcification, which was found in the Sham-operated group as well, and yet no inoculation-site injury has ever been reported. Our study revealed that stem cell transplantation can have a positive effect on behavioral recovery and reduction of infarct size, but the effect shown was no better than the effect of the exercise, which finding reconfirmed the importance of post-infarct rehabilitation. In addition, it was found that cell inoculation should be replaced by a noninvasive procedure.
Kim
Dae-Yul
DY
Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Park
Sung-Hye
SH
Lee
Si-Uk
SU
Choi
Deok-Hyung
DH
Park
Hee-Won
HW
Paek
Sun Ha
SH
Shin
Hye Young
HY
Kim
Eun-Young
EY
Park
Se-Pill
SP
Lim
Jin Ho
JH
D000818:Animals; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000534:rehabilitation* / Q000601:surgery*; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit