NCE

Under the 3 year grant award TR1-01232 titled ‘Mouse Models for Stem Cell Therapeutic Development’ we proposed to eliminate bottlenecks to the translation of stem cell research by a) developing a comprehensive collection of standardized mouse models on the appropriate immune backgrounds, and b) establishing production-scale processes to ensure their efficient availability to California researchers. This was a 3 year award which began November 2009 and was scheduled to conclude October 2012 however following the approval of our request for the extension of the award we have now completed the proposed work. This report will review the completed objectives.

The objectives of the study were to develop models of type 1 diabetes (T1D), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and myocardial infarct (MI); to characterize these models; and to develop operational processes to make these models available to the research community. Where feasible the models have been developed in the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mouse due to its highly immunocompromised status making it a favorable host for human cells and tissues. Additionally, the NSG mouse is also the platform on which our humanized immune system is built and offers the additional benefit of supporting stem cell therapy studies assessing the immunogenicity of novel stem cell therapeutics.

Objectives achieved to date include the release of the streptozotocin (STZ) model of T1D, the experimental autoimmune encephalomyelitis (EAE) myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP) models of MS and the methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) plus probenecid chronic model of PD. In this report, we have achieved goals of successfully completing Spinal Cord Injury (SCI) model, Traumatic Brain Injury (TBI) model, middle cerebral artery occlusion (MCAO) model of stroke and myocardial infarct (MI) model. Model reproducibility in each case is supported by histological assessment. All of these four models required surgical expertise obtained through extensive training.

As previously noted, characterization and optimization of models is only the first step in providing this resource to the research community. The expertise that is developed needs to be adequately shared so as to create redundancy within the JAX in vivo program and maintained so it is always readily available.