This application seeks support for a specialty board certified (ACVS) equine veterinarian to complete the final stages of preparation for her career as a translational clinical scientist in the fields of stem cell biology and regenerative medicine. Th applicant will work in the Cornell University induced Pluripotent Stem (iPS) Cell Core Laboratory under the guidance of the her mentor, Dr. Lisa A. Fortier, and collaborator, Dr. John C. Schimenti. Dr. Fortier is a scientist and large animal orthopedic surgeon who is well established in the fields of tendon repair and stem cell therapies. Dr. Schimenti is regarded as an expert in the fields of genetics and stem cell biology. Both have outstanding records for training graduate students and mentoring postdoctoral candidates and the overall research environment at Cornell is unique and eminently qualified to train translational scientists. The proposal is divide into two phases, a mentored phase and a transition phase into an independent research investigator. During Phase I, the applicant will complete her Ph.D. and seek to broaden her knowledge base and skill set to develop a deeper understanding of the basic biology of iPS cells, including their immunogenic and immunomodulatory properties compared to mesenchymal stem cells (MSCs). The applicant and her mentor have assembled a team of immunology collaborators, Drs. Douglas Antczak, Julia Felippe (Flaminio), and Cynthia Leifer, to advise the applicant during this mentored phase and help her learn the valuable immunology concepts and methods needed to complete these studies and understand their biological significance. In Phase II the applicant will apply the knowledge and skills learned in Phase I to complete a proof-of- principle in vivo study examining the early and late biological responses of diseased tendon to iPS cell and MSC treatment and the regenerative potential of iPS cells and MSCs for tendon repair. For these studies, we will use the well established equine model of tendonitis which has been extensively used by our research group. These experiments will test the hypothesis that iPS cells will have similar immunogenic and immunomodulatory properties as MSCs but superior regenerative potential because they are pluripotent stem cells whereas MSCs are not. This information is clinically important for determining which stem cell type should be applied therapeutically in the treatment of tendon diseases. The expectation of this proposal is that the applicant will gain the necessary laboratory research, scientific, and management skills necessary to establish a niche in the field of regenerative medicine as an independent clinician scientist in an academic environment.
The proposed research plan would generate and characterize equine induced pluripotent stem (iPS) cells including their ability to stimulate or decrease an immune response. The immune properties and regenerative potential of iPS cells would then be compared to mesenchymal stem cells (MSCs) using the well established equine model of tendonitis. The knowledge gained though the completion of these studies would provide immediately relevant, clinically applicable information for determining which stem cell type should be applied therapeutically for the treatment of tendonitis in people.
|Lang, Hayley M; Schnabel, Lauren V; Cassano, Jennifer M et al. (2017) Effect of needle diameter on the viability of equine bone marrow derived mesenchymal stem cells. Vet Surg 46:731-737|
|Berglund, Alix K; Fortier, Lisa A; Antczak, Douglas F et al. (2017) Immunoprivileged no more: measuring the immunogenicity of allogeneic adult mesenchymal stem cells. Stem Cell Res Ther 8:288|
|Berglund, A K; Schnabel, L V (2017) Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies. Equine Vet J 49:539-544|
|Pezzanite, Lynn M; Fortier, Lisa A; Antczak, Douglas F et al. (2015) Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo. Stem Cell Res Ther 6:54|
|Schnabel, Lauren V; Abratte, Christian M; Schimenti, John C et al. (2014) Induced pluripotent stem cells have similar immunogenic and more potent immunomodulatory properties compared with bone marrow-derived stromal cells in vitro. Regen Med 9:621-35|
|Schnabel, Lauren V; Pezzanite, Lynn M; Antczak, Douglas F et al. (2014) Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro. Stem Cell Res Ther 5:13|
|Schnabel, Lauren V; Abratte, Christian M; Schimenti, John C et al. (2012) Genetic background affects induced pluripotent stem cell generation. Stem Cell Res Ther 3:30|