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

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Massoud Vosough, Francesco Ravaioli, Mihaela Zabulica, Miriam Capri, Paolo Garagnani, Claudio Franceschi, Julie Piccand, Marine R.-C. Kraus, Kristina Kannisto, Roberto Gramignoli, Stephen C. Strom, Atsushi Asakura.


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.

Partial Text

Aging is accompanied by a significant decline in physiologic functions in several organs, and by a dramatic increase in disabilities. At the cellular level, a part of this decline is related to cell senescence [1,2]. During the past years, the scientific community faced an increasing demand in cell-based technologies aimed at treating disorders associated with aging to enable elderly people to lead healthy and more productive lives [3]. The introduction of cell fate-manipulating technologies for the remodeling of somatic cells into embryonic-like stem cells has opened the door to new studies in geriatric disorders. Human induced Pluripotent Stem Cells (iPSCs) have the potential to provide a nearly unlimited source of cells for basic research, and disease modeling [4].

Cellular reprogramming is a gradual course in which expression of endogenous genes linked to pluripotency are induced in somatic cells. However, such an approach is often inefficient, with limited success and generation of hiPSC was reported to be a stochastic process, where most of the differentiated cells fail to acquire a pluripotent state. [25–27].




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