1. Applying hydrodynamic pressure to efficiently generate induced pluripotent stem cells via reprogramming of centenarian skin fibroblasts
- Author
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Kristina Kannisto, Miriam Capri, Julie Piccand, Francesco Ravaioli, Paolo Garagnani, Claudio Franceschi, Mihaela Zabulica, Roberto Gramignoli, Stephen C. Strom, Marine R.-C. Kraus, Massoud Vosough, Vosough M., Ravaioli F., Zabulica M., Capri M., Garagnani P., Franceschi C., Piccand J., Kraus M.R.-C., Kannisto K., Gramignoli R., and Strom S.C.
- Subjects
Adult ,0301 basic medicine ,Somatic cell ,Science ,Genetic Vectors ,Induced Pluripotent Stem Cells ,Primary Cell Culture ,Biology ,Transfection ,Sendai virus ,Transplantation, Autologous ,Viral vector ,03 medical and health sciences ,Transduction (genetics) ,0302 clinical medicine ,Induced Pluripotent Stem Cells, Ageing, Pluripotency, Geriatrics ,Humans ,Cellular Reprogramming Techniques ,Vector (molecular biology) ,Induced pluripotent stem cell ,Cells, Cultured ,Skin ,Aged, 80 and over ,Cloning ,Multidisciplinary ,Regeneration (biology) ,Age Factors ,Infant, Newborn ,Reproducibility of Results ,Fibroblasts ,Cellular Reprogramming ,Skin Aging ,3. Good health ,Cell biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Hydrodynamics ,Medicine ,Reprogramming ,Research Article - Abstract
Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105–107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. In conclusion, dermal fibroblasts from human subjects older than 100 years can be efficiently and reproducibly reprogrammed to fully pluripotent cells with minor modifications to the standard reprogramming procedures. Efficient generation of iPSCs from the elderly may provide a source of cells for the regeneration of tissues and organs with autologous cells as well as cellular models for the study of aging, longevity and age-related diseases.
- Published
- 2019