Under the 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 are now scheduled to complete the proposed work by October 2013. This report will review the completed objectives and provide an update on those objectives still underway.
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 are to be 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.
Development of the SCI model is progressing noting that the surgical procedure has been mastered and technicians have been trained to execute related surgical aftercare and phenotyping tests. Characterization of the model has begun and is expected to be completed Q2.
Development of the stroke middle cerebral artery occlusion (MCAO) model is well underway with the surgical procedure optimization having been completed. Prior to initiating additional staff training our surgical technician is currently executing studies to verify infarct reproducibility.
The loss of our previous surgical team to graduate school has impacted the progression of work initiated on the TBI and MI models, requiring the training of new staff on all procedures from surgery to phenotype analysis. This retraining is underway and will be supported by Dr. Bonnie Lyons, Associate Veterinarian and head of surgical services for The Jackson Laboratory.
It has become clear to us that 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.