Research Paper Volume 6, Issue 12 pp 1094—1108

Aged iPSCs display an uncommon mitochondrial appearance and fail to undergo in vitro neurogenesis

Andrea Masotti1, , Antonella Celluzzi1, , Stefania Petrini2, , Enrico Bertini3, , Ginevra Zanni3, , Claudia Compagnucci3, ,

  • 1 Gene Expression–Microarrays Laboratory, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy
  • 2 Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy
  • 3 Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Piazza S. Onofrio, 4 00165 Rome, Italy

Received: September 5, 2014       Accepted: December 20, 2014       Published: December 30, 2014
How to Cite

Copyright: © 2014 Masotti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Reprogramming of human fibroblasts into induced pluripotent stem cells (iPSCs) leads to mitochondrial rejuvenation, making iPSCs a candidate model to study the mitochondrial biology during stemness and differentiation. At present, it is generally accepted that iPSCs can be maintained and propagated indefinitely in culture, but no specific studies have addressed this issue. In our study, we investigated features related to the 'biological age' of iPSCs, culturing and analyzing iPSCs kept for prolonged periods in vitro. We have demonstrated that aged iPSCs present an increased number of mitochondria per cell with an altered mitochondrial membrane potential and fail to properly undergo in vitro neurogenesis. In aged iPSCs we have also found an altered expression of genes relevant to mitochondria biogenesis. Overall, our results shed light on the mitochondrial biology of young and aged iPSCs and explore how an altered mitochondrial status may influence neuronal differentiation. Our work suggests to deepen the understanding of the iPSCs biology before considering their use in clinical applications.


iPSCs: induced pluripotent stem cells; a-iPSCs: aged-iPSCs; y-iPSCs: young-iPSCs.