Teratogenic Potential in Cultures Optimized for Oligodendrocyte Development from Mouse Embryonic Stem Cells
| Autor: | Mary E. Kiel, Dorota Sadowski, Marisa Apicella, Randall D. McKinnon, Cui Ping Chen, Aileen G. Arriola |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Neurogenesis
Population Cell Culture Techniques Drug Evaluation Preclinical Embryoid body Biology Models Biological Mice medicine Animals Noggin education Cells Cultured Embryonic Stem Cells reproductive and urinary physiology Platelet-Derived Growth Factor education.field_of_study Neuroectoderm Mesenchymal stem cell Gene Expression Regulation Developmental Cell Differentiation Cell Biology Hematology Embryonic stem cell Oligodendrocyte Cell biology Oligodendroglia Teratogens medicine.anatomical_structure Culture Media Conditioned Calibration embryonic structures Immunology Fibroblast Growth Factor 2 biological phenomena cell phenomena and immunity Neural development Developmental Biology |
| Zdroj: | Stem Cells and Development. 19:1343-1353 |
| ISSN: | 1557-8534 1547-3287 |
| Popis: | We describe a rapid and efficient 5-step program of defined factors for the genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors promoting neural induction (retinoids, noggin) are required, while exogenous Sonic hedgehog is not. In contrast we were unable to generate OLs by trans-differentiation of ethically neutral mesenchymal stem cells, indicating a requirement for cis-differentiation via neural ectoderm for OL genesis. In the ESC-derived cultures, our optimized protocol generated a mixed population with 49% O4(+), Olig2(+) OL lineage cells. These cultures also retained pluripotential markers including Oct4, and an analysis of embryoid body formation in vitro, and allogeneic grafts in vivo, revealed that the ESC-derived cultures also retained teratogenic cells. The frequency of embryoid body formation from terminal differentiated OL cultures was 0.001%, 100-fold lower than that from ESCs. Our results provide the first quantitative measurement of teratogenicity in ESC-derived, exhaustively differentiated allogeneic grafts, and demonstrate the unequivocal need to purify ESC-derived cells in order to generate a safe population for regenerative therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|