Donor genetic backgrounds contribute to the functional heterogeneity of stem cells and clinical outcomes
Ting Wang, Juan Zhang, Jinqi Liao, Fan Zhang, Guangqian Zhou
Abstract
Abstract Stable and sustainable stem cell sources for stem cell-based therapies are scarce and a key bottleneck for clinical applications. The regenerative potential of stem cells is usually attributed to several allogeneic or even autologous donor-related factors. Genetic background and epigenetic variations in different individuals may significantly affect the functional heterogeneity of stem cells. Particularly, single-nucleotide polymorphisms (SNPs) have been implicated in diseases with monogenetic or multifactorial and complex genetic etiologies. However, the possible effects of individual SNPs on donor stem cells remain far from fully elucidated. In this Perspective, we will discuss the roles played by donor genetic traits in the functional heterogeneity of induced pluripotent stem cells, mesenchymal stem cells, and hematopoietic stem cells and their implications for regenerative medicine and therapy. Significance statement In the past decades, thousands of genetic variations termed single-nucleotide polymorphisms (SNPs) have been identified, many of which are likely associated with complex human diseases that were previously hypothesized to have other unique genetic drivers. Genetic studies are rapidly being extended to stem cell research and regenerative medicine models. Considering the impact of SNPs in the etiology of diseases, it is reasonable to consider that stem cells carrying disease-associated SNPs should not be transplanted onto the recipients with the same disease.