T. Pivneva and G. Skibo contributed equally to this work.
Long-term fate of grafted hippocampal neural progenitor cells following ischemic injury
Article first published online: 22 APR 2014
© 2014 Wiley Periodicals, Inc.
Journal of Neuroscience Research
Volume 92, Issue 8, pages 964–974, August 2014
How to Cite
Tsupykov, O., Kyryk, V., Smozhanik, E., Rybachuk, O., Butenko, G., Pivneva, T. and Skibo, G. (2014), Long-term fate of grafted hippocampal neural progenitor cells following ischemic injury. J. Neurosci. Res., 92: 964–974. doi: 10.1002/jnr.23386
- Issue published online: 13 JUN 2014
- Article first published online: 22 APR 2014
- Manuscript Accepted: 24 FEB 2014
- Manuscript Revised: 30 JAN 2014
- Manuscript Received: 29 NOV 2013
- State Key Laboratory of Molecular and Cellular Biology . Grant Number: DFFD F 46.2/001.
- stem cells;
- cerebral ischemia;
The adult CNS has a very limited capacity to regenerate neurons after insult. To overcome this limitation, the transplantation of neural progenitor cells (NPCs) has developed into a key strategy for neuronal replacement. This study assesses the long-term survival, migration, differentiation, and functional outcome of NPCs transplanted into the ischemic murine brain. Hippocampal neural progenitors were isolated from FVB-Cg-Tg(GFPU)5Nagy/J transgenic mice expressing green fluorescent protein (GFP). Syngeneic GFP-positive NPCs were stereotactically transplanted into the hippocampus of FVB mice following a transient global cerebral ischemia model. Behavioral tests revealed that ischemia/reperfusion induced spatial learning disturbances in the experimental animals. The NPC transplantation promoted cognitive function recovery after ischemic injury. To study the long-term fate of grafted GFP-positive NPCs in a host brain, immunohistochemical approaches were applied. Confocal microscopy revealed that grafted cells survived in the recipient tissue for 90 days following transplantation and differentiated into mature neurons with extensive dendritic trees and apparent spines. Immunoelectron microscopy confirmed the formation of synapses between the transplanted GFP-positive cells and host neurons that may be one of the factors underlying cognitive function recovery. Repair and functional recovery following brain damage represent a major challenge for current clinical and basic research. Our results provide insight into the therapeutic potential of transplanted hippocampal progenitor cells following ischemic brain injury. © 2014 Wiley Periodicals, Inc.