Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain.
OBJECTIVE
Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation.


METHODS
Multipotential NPCs were generated from ESCs by using the stromal cell-derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 +/-2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 +/- 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)-positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, beta-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 +/-11.5% were positive for glutamate decarboxylase, 13.3 +/- 5.8% for glutamate, 2.1 +/- 2.5% for tyrosine hydroxylase, 1.8 +/- 2% for serotonin, and 0.4 +/- 0.2% for choline acetyltransferase.


CONCLUSIONS
The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.
Takagi
Yasushi
Y
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ytakagi@kuhp.kyoto-u.ac.jp
Nishimura
Masaki
M
Morizane
Asuka
A
Takahashi
Jun
J
Nozaki
Kazuhiko
K
Hayashi
Junya
J
Hashimoto
Nobuo
N
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002545:Brain Ischemia / Q000628:therapy* / Q000662:veterinary; D002454:Cell Differentiation; D002470:Cell Survival; D049452:Green Fluorescent Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons; D018377:Neurotransmitter Agents / Q000096:biosynthesis; D033581:Stem Cell Transplantation / Q000662:veterinary
D015415:Biomarkers; D018377:Neurotransmitter Agents; D049452:Green Fluorescent Proteins