Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (Cyno-1) after transplantation Journal Article
| Authors: | Sanchez-Pernaute, R.; Studer, L.; Ferrari, D.; Perrier, A.; Lee, H.; Viñuela, A.; Isacson, O. |
| Article Title: | Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (Cyno-1) after transplantation |
| Abstract: | Dopamine (DA) neurons can be derived from human and primate embryonic stem (ES) cells in vitro. An ES cell-based replacement therapy for patients with Parkinson's disease requires that in vitro-generated neurons maintain their phenotype in vivo. Other critical issues relate to their proliferative capacity and risk of tumor formation, and the capability of migration and integration in the adult mammalian brain. Neural induction was achieved by coculture of primate parthenogenetic ES cells (Cyno-1) with stromal cells, followed by sequential exposure to midbrain patterning and differentiation factors to favor DA phenotypic specification. Differentiated ES cells were treated with mitomycin C and transplanted into adult immunosuppressed rodents and into a primate (allograft) without immunosuppression. A small percentageof DA neurons survived in both rodent and primate hosts for the entire term of the study (4 and 7 months, respectively). Other neuronal and glial populations derived from Cyno-1 ES cells showed, in vivo, phenotypic characteristics and growth and migration patterns similar to fetal primate transplants, and a majority of cells (>80%) expressed the forebrain transcription factor brain factor 1. No teratoma formation was observed. In this study, we demonstrate long-term survival of DA neurons obtained in vitro from primate ES cells. Optimization of differentiation, cell selection, and cell transfer is required for functional studies of ES-derived DA neurons for future therapeutic applications. ©AlphaMed Press. |
| Keywords: | immunohistochemistry; controlled study; allograft; unclassified drug; nonhuman; cell proliferation; animal cell; phenotype; mammalia; animals; animal tissue; cell survival; cells, cultured; cell growth; embryo; embryonic stem cell; cell line; glial fibrillary acidic protein; sonic hedgehog protein; animal experiment; animal model; transcription factor; stem cell transplantation; in vivo study; cell differentiation; neurons; in vitro study; transplantation; telomerase; time factors; alkaline phosphatase; tyrosine 3 monooxygenase; brain derived neurotrophic factor; rat; cell migration; cell movement; glia cell; stem cells; mitomycin c; microscopy, fluorescence; teratoma; rats; mesencephalon; rodentia; rats, sprague-dawley; parkinson disease; stroma cell; primate; macaca; forebrain; octamer transcription factor 4; immunosuppressive agents; dopamine; dopaminergic nerve cell; cell transfer; cell selection; differentiation; corpus striatum; fibroblast growth factor 8; transforming growth factor beta3; embryonic stem (es) cell; macaca fascicularis; glial cell line derived neurotrophic factor; primates; cell nucleus antigen; parkinson's disease; parthenogenesis; tumor rejection antigen; stereometry; 1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine; brain factor 1; stage specific embryo antigen 4; vesicular monoamine transporter 2; cell strain cyno 1 |
| Journal Title: | Stem Cells |
| Volume: | 23 |
| Issue: | 7 |
| ISSN: | 1066-5099 |
| Publisher: | AlphaMed Press |
| Date Published: | 2005-08-01 |
| Start Page: | 914 |
| End Page: | 922 |
| Language: | English |
| DOI: | 10.1634/stemcells.2004-0172 |
| PUBMED: | 15941857 |
| PROVIDER: | scopus |
| PMCID: | PMC2654596 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 70" - "Export Date: 24 October 2012" - "CODEN: STCEE" - "Source: Scopus" |
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