Donor genetic backgrounds contribute to the functional heterogeneity of stem cells and clinical outcomes

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.