Trophism of neural progenitor cells to embryonic stem cells: neural induction and transplantation in a mouse ischemic stroke model.
Embryonic stem cell (ESC)-derived products have emerged as a promising cell source for neuroregeneration. C17.2 neural precursor cells were noted to express genes of neurotrophins and neuroprotective factors and to be enable to enhance proliferation, neuritogenesis, and differentiation of SH-SY5Y and SK-N-AS neuroblasts, suggesting their neurotrophic potential. We used C17.2 cells as neurotrophic chaperones to induce ESCs, D3, and E14TG2a into neural lineage cells. Significantly greater numbers of Sox-2(+), Musashi-1(+), and nestin(+) neurospheres developed in noncontact cocultures than in cultures of ESCs without C17.2 support or with 50% conditioned medium after 8 days. Immunoreactivity of the neuronal, astrocytic and oligodendrocytic markers was evident in cultures further differentiated for 10 days. Expression of Pax-6, Otx-1, and Nurr-1 genes suggested neuroectodermal precursors in products encompassing neural stem cells, dopaminergic neurons, astrocytes, and oligodendrocytes. Alpha-fetoprotein, GATA-4, Brachyury, Nkx-2.5, and Myf-5 genes were not detected, indicating any mesodermal and endodermal cells. However, weak expression of Oct-4 was noted. Behavioral assessment of ischemic mice 2 weeks after transplantation revealed significant improvement in cognitive function compared with that in ischemic sham-operated mice. Tracking bromodeoxyuridine-labeled products demonstrated that mostly implanted cells were localized along the needle track of the injection in the brain parenchyma, whereas some migrated to the striatum, cortex, nerve fiber bundle of the corpus callosum, and hippocampus in the ipsilateral hemisphere. One episode (of 22) of teratoma development was noted. Data from this study suggest a paradigm of trophism of neural progenitor cells for induction of ESCs into neural lineage cells.
Fong
Shu Pan
SP
Department of Anatomical & Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.
Tsang
Kam Sze
KS
Chan
Amy Bik Wan
AB
Lu
Gang
G
Poon
Wai Sang
WS
Li
Karen
K
Baum
Larry William
LW
Ng
Ho Keung
HK
D000818:Animals; D000963:Antimetabolites; D002545:Brain Ischemia / Q000150:complications / Q000628:therapy*; D001973:Bromodeoxyuridine; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement; D017690:Cell Transplantation / Q000502:physiology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003627:Data Interpretation, Statistical; D053595:Embryonic Stem Cells / Q000502:physiology* / Q000637:transplantation*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000502:physiology* / Q000637:transplantation*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D020521:Stroke / Q000209:etiology / Q000628:therapy*
D000963:Antimetabolites; D017077:Culture Media, Conditioned; D001973:Bromodeoxyuridine