TY - JOUR
T1 - Behavioral improvement after transplantation of neural precursors derived from embryonic stem cells into the globally ischemic brain of adolescent rats
AU - Kang, Hoon Chul
AU - Kim, Dae Sung
AU - Kim, Ji Young
AU - Kim, Han Soo
AU - Lim, Bo Young
AU - Kim, Heung Dong
AU - Lee, Jin Sung
AU - Eun, Baik Lin
AU - Kim, Dong Wook
N1 - Funding Information:
This work was supported by the 2008 scientific (Seokchun) Fund Award of the Korean Society of Pediatrics and by Grant SC2130 and SC1110 from the Stem Cell Research Center of the 21st Century Frontier Research Program which is funded by the Ministry of Education, Science, and Technology, Republic of Korea. We thank Anna-Katerina Hadjantonakis in Sloan-Kettering Institute for providing ES cells with EYFP.
PY - 2010/9
Y1 - 2010/9
N2 - Purpose: We intended to determine whether transplanted neural precursors, derived from mouse embryonic stem (ES) cells, can migrate and differentiate into mature neurons and glial cells in damaged brains and improve functional deficits caused by global cerebral ischemic injury in adolescent rats. Methods: Global ischemia was induced using the four-vessel occlusion method. ES cells that display enhanced expression of yellow fluorescent protein were co-cultured in N2 supplemented media with PA6 cells that had stromal derived inducing activity. Neural precursor cells were directly transplanted bilaterally into hippocampal C3 areas 2. weeks after induction of global ischemia. Assessments of the Morris water-maze test at eight weeks and, the Open field activity levels at two, four, six and eight weeks after transplantation were carried out according to standard methods. Results: From neural precursors, we were able to generate neural lineages, including neurons and glial cells in vitro. Eight weeks following transplantation, cellular migration as well as generation of neural cells including neurons, astrocytes, and oligodendrocytes developed from the grafted ES cell-derived neural precursors were observed. Cell-transplanted animals exhibited enhanced functional recovery on sensorimotor and behavioral tests, compared to vehicle-treated control animals. Conclusion: Therefore, transplantation of mouse ES cell-derived neural precursor cells shows promise for improving recovery after global ischemia in adolescent rats.
AB - Purpose: We intended to determine whether transplanted neural precursors, derived from mouse embryonic stem (ES) cells, can migrate and differentiate into mature neurons and glial cells in damaged brains and improve functional deficits caused by global cerebral ischemic injury in adolescent rats. Methods: Global ischemia was induced using the four-vessel occlusion method. ES cells that display enhanced expression of yellow fluorescent protein were co-cultured in N2 supplemented media with PA6 cells that had stromal derived inducing activity. Neural precursor cells were directly transplanted bilaterally into hippocampal C3 areas 2. weeks after induction of global ischemia. Assessments of the Morris water-maze test at eight weeks and, the Open field activity levels at two, four, six and eight weeks after transplantation were carried out according to standard methods. Results: From neural precursors, we were able to generate neural lineages, including neurons and glial cells in vitro. Eight weeks following transplantation, cellular migration as well as generation of neural cells including neurons, astrocytes, and oligodendrocytes developed from the grafted ES cell-derived neural precursors were observed. Cell-transplanted animals exhibited enhanced functional recovery on sensorimotor and behavioral tests, compared to vehicle-treated control animals. Conclusion: Therefore, transplantation of mouse ES cell-derived neural precursor cells shows promise for improving recovery after global ischemia in adolescent rats.
KW - Cell transplantation
KW - Embryonic stem cells
KW - Globally ischemic brain
KW - Neural precursors
UR - http://www.scopus.com/inward/record.url?scp=77955424796&partnerID=8YFLogxK
U2 - 10.1016/j.braindev.2009.09.010
DO - 10.1016/j.braindev.2009.09.010
M3 - Article
C2 - 19854013
AN - SCOPUS:77955424796
SN - 0387-7604
VL - 32
SP - 658
EP - 668
JO - Brain and Development
JF - Brain and Development
IS - 8
ER -