The influence of donor age on induced pluripotent stem cell functionality

This 2018 German review subject was the influence of donor age on induced pluripotent stem cell functionality:

“Induced pluripotent stem cells (iPSCs) avoid many of the restrictions that hamper the application of human embryonic stem cells. Also, the donor’s clinical phenotype is often known when working with iPSCs.

Typical signs of cellular ageing are reverted in the process of iPSC reprogramming, and iPSCs from older donors do not show diminished differentiation potential nor do iPSC-derived cells from older donors suffer early senescence or show functional impairments when compared with those from younger donors.”

The reviewers discussed limitations in the current research:

  • “Mutations in nuclear and mitochondrial DNA acquired over the donor’s lifespan and during the reprogramming process might persist.
  • It is not yet known how strongly the variable genetic background of individual donors affects the reprogramming process and the quality of resulting iPSCs.
  • A low number of donors and cell lines is a general problem in almost all research articles on the topic of iPSCs. This combined with the lack of a standardised protocol for optimal iPSC derivation, culture and quality control makes any comparison between different publications very difficult if not impossible. Especially, since it has been shown that many factors influence the quality of iPSCs and iPSC-derived cells, such as time and cell type used for reprogramming, time in culture, or reprogramming modality.
  • A problem lies in the retention of tissue-specific epigenetic alterations which in part could be caused by incomplete reprogramming and might be improved by vigorous quality testing and careful selection of iPSC colonies during reprogramming and passaging.
  • The question regarding tumourigenicity will most likely only be answered satisfactorily once 1) the differentiation methods are further improved, 2) iPSC-derived cell-based therapies have made their way further into clinical practice, and 3) patients receiving treatments have been observed for multiple years.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790033/pdf/fcvm-05-00004.pdf “Age Is Relative-Impact of Donor Age on Induced Pluripotent Stem Cell-Derived Cell Functionality”

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