A Novel Approach for Determining the Critical Quality Attributes of Mesenchymal Stem Cells by Specifying Cell Population With Replication Potential.

We introduce a novel approach to determine the critical quality attributes (CQAs) of mesenchymal stem cells (MSCs) expected to exert immunosuppressive effects. MSCs retained homeostatic replication potentials, such as sustainable growth and consistent cell morphology as a population, in early passages, but lost them in late passages. Characteristic surface markers of MSCs (ie, CD73, CD90, and CD105) were no longer expressed at 2 weeks after subcutaneous transplantation into NOG mice when MSCs from late passages were transplanted, but not when MSCs from early passages were transplanted, suggesting that the biological effects of the MSCs differed according to the timing of cell harvesting and highlighting the importance of specifying MSCs that retained homeostatic features to define the CQAs.

Improving the differentiation potential of pluripotent stem cells by optimizing culture conditions.

Embryoid cells and induced pluripotent stem cells (iPSCs) are pluripotent stem cells (PSCs). They retain differentiation and self-renewal potential. However, the differentiation potential of PSCs can be changed by the culture medium.

Kynurenine signaling through the aryl hydrocarbon receptor maintains the undifferentiated state of human embryonic stem cells.

Kynurenine, which is generated from tryptophan by indoleamine 2,3-dioxygenase 1 (IDO1), binds to the aryl hydrocarbon receptor (AhR). Here, we report that kynurenine was produced by undifferentiated human embryonic stem cells (hESCs) and by induced pluripotent stem cells (iPSCs). In undifferentiated hESCs, kynurenine stimulated the AhR to promote the expression of self-renewal genes.