Changes in adult fibroblast populations with passaging reduce reprogramming efficiency

Abstract

Induced pluripotent stem cell (iPSC) technology has immense therapeutic potential to treat injury and a variety of degenerative diseases. Previous research has suggested an elite model for the reprogramming of adult fibroblasts into iPSCs; in this model, a rare existing population of primary cells preferentially reprogram to pluripotency. While it is postulated that this elite population of cells could have adult stem cell origins, few studies have been able to identify the key attributes of such populations. Here, we explore the “reprogrammability” of a new adult stem cell population and study how changes in these cells over time (i.e. higher passages) undergo phenotypic changes that may contribute to decreased reprogramming efficiency. Preliminary results indicate a significantly higher reprogramming efficiency in lower passage cells; these data suggest that population changes and perhaps differentiation of progenitor cells in higher passages result in decreased number of “elite”, reprogrammable cells. This model is important for evaluating reprogramming mechanisms as well as for culture techniques for future clinical applications.Grant Funding Source: CIRM