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PLoS One. 2019 Apr 25;14(4):e0215490. doi: 10.1371/journal.pone.0215490. eCollection 2019.

Applying hydrodynamic pressure to efficiently generate induced pluripotent stem cells via reprogramming of centenarian skin fibroblasts.

Author information

Department of Stem Cells and Developmental Biology, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Bologna, Italy.
Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
CIG, Interdepartmental Center 'L. Galvani', Alma Mater Studiorum, Bologna, Italy.
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
CNR, Institute of Molecular Genetics, IGM, Unit. Bologna, Bologna, Italy.
IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Nestlé Institute of Health Sciences, Stem Cells, Lausanne, Switzerland.


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.

Conflict of interest statement

All authors declare no competing interest relevant to the submitted research. Research funding was provided entirely by EU FP7 grant HUMAN (Health and the Understanding of Metabolism, Aging and Nutrition)(grant agreement: 602757) and Vetenskaprådet (Swedish Research Council) and the Törsten and Ragnar Söderberg stiftelsen as indicated in the Amended Funding Statement. Nestlé SA does not hold any patent, product in development, or marketed product related to the research described in the manuscript. Nestlé Institute of Health Science (Nestlé S.A) employed authors Julie Piccand and Marie R. C. Kraus at the time of manuscript submission. Nestlé SA did not provide economical support for study design, data collection and analysis. JP and MK contributions are articulated in the “author contribution” section. Involvement of Nestlé SA in the research does not alter adherence to PLOS ONE policies on sharing data and methods.

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