Year 3

The fate, migration, and repair potential of a stem cell is driven by a combination of intrinsic properties, such as the type, source, and maintenance/differentiation of the cell in vitro, as well as extrinsic factors the cell encounters in the in vivo environment, such as proteins related to inflammation or the growth matrix. Variations in the intrinsic properties of the cell may affect the potential of that cell for uncontrolled proliferation or the response of the cell to extrinsic factors that it encounters in its environment. We have previously shown that neural stem cells derived from human fetal tissue are highly sensitive to extrinsic inflammatory signals in vitro and in vivo. In the current studies, we sought to determine whether neural stem cell populations derived from different sources respond to the same sorts of inflammatory signals, in other words, whether these extrinsic factors affect stem cells as a general principal. Accordingly, we sought to characterize the intrinsic properties of neural stem cells derived from different sources and exposed to extrinsic inflammatory signals, including human embryonic and induced pluripotent cell, as an essential component of understanding of basic stem cell biology. We found that, in fact, all neural stem cells derived from embryonic and induced pluripotent populations responded to inflammatory signals. However, we also found that cell line intrinsic properties exert a strong degree of control, in some cases resulting in opposing consequences for cell proliferation and fate. Critically, we found that in vitro characteristics of response to extrinsic inflammatory signals were predictive for the way different cell populations behaved in vivo after transplantation. These data may offer a new opportunity to screen stem cell populations in vitro for comparability and predicted in vivo translational properties, and reveal a new and critical set of interactions between intrinsic cell programming and response to the environment.