The Journal of clinical investigation, 2011-06, Vol.121 (6), p.2326-2335
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease
- Ist Teil von
- The Journal of clinical investigation, 2011-06, Vol.121 (6), p.2326-2335
- Ort / Verlag
- United States: American Society for Clinical Investigation
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Parkinson disease (PD) involves the selective loss of midbrain dopamine (mDA) neurons and is a possible target disease for stem cell-based therapy. Human induced pluripotent stem cells (hiPSCs) are a potentially unlimited source of patient-specific cells for transplantation. However, it is critical to evaluate the safety of hiPSCs generated by different reprogramming methods. Here, we compared multiple hiPSC lines derived by virus- and protein-based reprogramming to human ES cells (hESCs). Neuronal precursor cells (NPCs) and dopamine (DA) neurons delivered from lentivirus-based hiPSCs exhibited residual expression of exogenous reprogramming genes, but those cells derived from retrovirus- and protein-based hiPSCs did not. Furthermore, NPCs derived from virus-based hiPSCs exhibited early senescence and apoptotic cell death during passaging, which was preceded by abrupt induction of p53. In contrast, NPCs derived from hESCs and protein-based hiPSCs were highly expandable without senescence. DA neurons derived from protein-based hiPSCs exhibited gene expression, physiological, and electrophysiological properties similar to those of mDA neurons. Transplantation of these cells into rats with striatal lesions, a model of PD, significantly rescued motor deficits. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of PD.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9738eISSN: 1558-8238DOI: 10.1172/jci45794Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3104759
- Format
- –
- Schlagworte
- Animals, Apoptosis, Arginine, Biomedical research, Cell Differentiation, Cell Line - transplantation, Cell Lineage, Cellular Reprogramming, Cellular Senescence, Dopamine - metabolism, Gene Expression Regulation, Developmental, Genes, p53, Genetic Vectors - pharmacology, Humans, Induced Pluripotent Stem Cells - physiology, Induced Pluripotent Stem Cells - transplantation, Kruppel-Like Transcription Factors - genetics, Kruppel-Like Transcription Factors - physiology, Lentivirus - physiology, Neurons, Neurons - cytology, Neurons - metabolism, Octamer Transcription Factor-3 - genetics, Octamer Transcription Factor-3 - physiology, Parkinson's disease, Parkinsonian Disorders - surgery, Phenols, Proto-Oncogene Proteins c-myc - genetics, Proto-Oncogene Proteins c-myc - physiology, Rats, Retroviridae - physiology, SOXB1 Transcription Factors - genetics, SOXB1 Transcription Factors - physiology, Tumor Suppressor Protein p53 - biosynthesis