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.
Bibliographical noteFunding 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.
All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health
- Developmental Neuroscience
- Clinical Neurology