Abstract

Public and private human stem cell banking institutions are currently hosting hundreds of thousands partially characterized cell populations, including a significant number of human pluripotent stem cell lines. To be considered for use in clinical applications, stem cell preparations must undergo rigorous testing in order to ensure safety for the recipient. With development of the methodologies for in vitro derivation, ex vivo maintenance and expansion of stem cells and targeted differentiation of multipotent and pluripotent stem cells, many novel issues were added to the list of safety concerns of cell and tissue preparations. These issues are related to the potential changes that may occur in the course of in vitro propagation of stem cells and cell-derived products, how these changes may affect the quality of the preparation; and the potential effects on the recipient. Only a limited number of studies about the role of subtle variations of individual capacity for repair of genotoxic damage in maintenance in vitro of human stem cells are currently available. Nevertheless, the assessment of individual repair capacity may play a crucial role in the safety of use of human stem cells, as it constitutes a major factor in the risk of occurrence of genomic alterations that may seriously compromise the quality of the product. This article reviews the available data about the role of individual capacity for DNA damage repair in different human stem cell types and the potential adverse effects that may occur with the use of cell preparations with inferior repair capacity.

Highlights

  • It may be advisable to include molecular analysis of the capacity to detect and repair DNA damage in the panels for analysis of safety of cell and cell-derived preparations for transplantation purposes

  • These issues are related to the potential changes that may occur in the course of in vitro propagation of stem cells and cell-derived products, how these changes may affect the quality of the preparation; and the potential effects on the recipient

  • Assessment of the individual capacity for DNA repair/maintenance of genomic integrity may assist in the screening of potential patients to differentiate between patients that may be eligible for transplantations of autologous induced pluripotent stem cell (iPSC)-derived cells and patients that may benefit from cell preparations from allogeneic iPSCs

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Summary

Introduction

It may be advisable to include molecular analysis of the capacity to detect and repair DNA damage in the panels for analysis of safety of cell and cell-derived preparations for transplantation purposes. The data about the role of individual capacity for repair of DNA/maintenance of genomic integrity for the outcomes of transplantations of stem cells other than HPSCs are still sparse.

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