Year 2
Although the role of the host immune response has been considered in the context of immune-rejection, predominantly regarding the T-cell response, the consequence of an ongoing inflammatory response within the context of the tissue microenvironment for cell fate, migration, and integration/efficacy has been largely overlooked. While classical immunosuppressants alter the T-cell response, these drugs have minimal impact on other immune cells such as neutrophils (polymorphonuclear (PMN) leukocytes) and macrophages (MACs)/microglia, which makes up a significant part of the host environment after traumatic injuries to the CNS, such as spinal cord injury (SCI). Accordingly, there is little known about the basic biology of either the host microenvironment or inflammatory microenvironment in influencing and interacting with either endogenous or transplanted stem cell populations. Understanding the molecules and signaling pathways directing hNSC fate choices in the injured CNS microenvironment is critical. hNSC derived from hiPS-NSC and hESC will be tested. We have therefore established and characterized hiPS-NSC and hES-NSC derived from multiple origins and tested the specific role of innate inflammatory cells (i.e. PMNs and macrophages) and molecules in cell fate, migration and proliferation of these hiPS-NSC and hES-NSC lines in vitro. Thus far, these data have revealed clear cell line specific intrinsic differences in response to inflammatory factors, which we will further investigated in the coming funding period both in vitro and in vivo.