Year 1

This progress report covers the 12 month period since the funding of this grant titled ‘Mouse Models for Stem Cell Therapeutic Development’. Under this grant awarded TR1-01232 we proposed to eliminate bottlenecks to 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.

Aims for year 1 include: 1. completion of validation and characterization of the type 1 diabetes model and its release; 2. optimization of the protocol for induction of Parkinson’s disease using the chronic MPTP-probenecid protocol and characterization of the behavioral phenotype; 3. optimization of the Multiple Sclerosis (MS) experimental autoimmune encephalomyelitis (EAE) induction protocol and characterization of the behavioral phenotype; and initiation of the development of the stroke surgical model.

We have completed the development of the streptozotocin induced type 1 diabetes model. We have optimized the concentration and dosing regimen required for induction of chronic hyperglycemia and validated the use of insulin producing cells for amelioration of hyperglycemia. We have also verified the stability of the hyperglycemic phenotype in NSG and their response to the transplantation of insulin producing cells following shipment. Current we have mice being maintained on the shelf in a normoglycemis state to determine the survival time for the graft.

We have completed the optimization of the concentration and dosing regimen for induction of Parkinson’s disease in the NSG mouse using the chronic MPTP and probenecid protocol and we have established the behavioral phenotype of the model. We are currently scaling up the model and validating the phenotype following shipment.

We have completed the optimization of two models for induction of EAE MS using Proteolipid Protein and Myelin-oligodendrocyte glycoprotein. We are now establishing the reproducibility of the models on scale up. The rapid induction hinders the potential to develop this model for shipment and we are currently reviewing options for modifying the model to address this concern.

All the models mentioned above although not yet fully released to the research community are ready for release and we are working with researchers interested in developing the models within their own facilities and researchers who are interested in working with JAX to execute studies using these models.

Due to the unexpected death of our surgeon we adjusted our first year aims regarding surgical models. The initiation of the development of traumatic brain injury (TBI) model was moved to year 1 in place of stroke. This change was made as it allowed us to leverage the expertise of Dr. Hall and our newly hired lab manager. Training has initiated in the surgical manipulation for injury induction and is proceeding without complication.

We have met the primary goals of year 1 have initiated work on goals set for year 2.