Radiation-Induced Disruption of Neural Stem Cell Migration

Pragathi Achanta, PhD
Postdoctoral Research Fellow

Introduction:


Neural stem cells reside in the subventricular zone of the brain. It is a key location for adult neurogenesis. When a patient receives whole brain, or even targeted radiation, the subventricular zone in many cases receives a substantial dose of radiotherapy as well. While a great deal is known about how radiation affects stem cells, very little is known about the effects of radiation on migration of new born cells. Since these new born stem cells may be recruited to the tumor, and may even attack the tumor cells, more must be studied about the effects that radiation has upon these cells’ migratory capabilities.


Aims/Goals:


Our research includes plans to determine the ability of radiation to arrest the migration of progenitor cells along an established pathway, to measure the effect of local radiation on stem cells in the subventricular zone and on their microenvironment, and to determine whether new born stem cells are attracted to a site of radiation damage and/or tumor altering their established migration paths, and identify underlying micro environmental factors and molecular pathways. A second aspect of therapeutic neural stem cells that we will investigate is how radiation alters the ability of endogenous neural stem cells to participate in repair.


Current Progress:


We have found that irradiation of the subventricular zone in the brain eliminates the dividing neural stem cells. We have also observed that radiation has a strong inhibitory effect on the migration of newborn cells. We are currently in the process of understanding if the newborn stem cells follow alternate migratory paths or if they die in the irradiated environment.


Clinical Implications/Relate to Patients:


Our results will directly inform clinical trials in the near future. Future trials may include, for example, a prospective trial to assess the efficacy of stem cell sparing radiation for which our data will provide important information on dose/volume endpoints. Another trial might combine radiation with molecular or pharmacological agents to promote neural progenitor cell survival, migration and differentiation.