The long-term goal of Yasuhiro Ikeda, D.V.M., Ph.D., is to develop efficient and safe gene and cell therapy platforms for diabetes and hypertensive heart disease.
Dr. Ikeda's main research interests include:
- Generation of embryonic stem cell-like stem cells from patients' skin and blood cells (induced pluripotent stem [iPS] cell technology)
- Generation of insulin-producing cells from iPS cells as novel cell therapy for diabetes
- Development of pancreatic islet-targeted gene transfer vectors for diabetes gene therapy
- Use of heart-targeted cardiac hormone gene therapy for hypertension and hypertensive heart disease
- Stem cell therapy for diabetes. iPS cell technology allows generation of embryonic stem cell-like cells from skin and blood cells of patients. Successful differentiation of patient-derived iPS cells into insulin-producing cells can lead to novel cell therapy for diabetes. Dr. Ikeda's lab has demonstrated generation of glucose-responsive, insulin-producing cells from iPS cells from diabetic patients. The lab was also able to regenerate human pancreatic islets in vivo using blood-derived iPS cells.
Dr. Ikeda and his team are currently working to improve the safety and efficiency of generating insulin-producing cells. They are also testing the therapeutic effects of iPS cell-derived insulin-producing cells in a diabetic model.
- Gene therapy for diabetes. Dr. Ikeda's lab has developed a novel gene transfer vector system that allows targeted gene delivery into pancreatic beta cells. The lab showed that pancreas-targeted expression of beta cell regenerating factors or immunomodulatory factors prevented mice from developing diabetes. Dr. Ikeda and his team are going to translate this technology for future diabetes gene therapy.
- Gene therapy for hypertensive heart disease. A frequent clinical phenotype of cardiac disease is diastolic dysfunction associated with high blood pressure (hypertension), which over time leads to profound cardiac remodeling and fibrosis (hypertensive heart disease) and progression to heart failure.
B-type natriuretic peptide (BNP) has blood pressure lowering, anti-fibrotic and anti-hypertrophic properties, making it an attractive therapeutic for attenuating the adverse cardiac remodeling associated with hypertension. However, use of natriuretic peptides for chronic therapy has been limited by their extremely short in vivo half-life.
Recently, Dr. Ikeda and his team used a novel heart-targeted gene transfer vector to deliver BNP and demonstrated that long-term cardiac BNP expression significantly lowered blood pressure, improved cardiac functions and extended the survival of rats with hypertensive heart disease. The lab is currently examining the feasibility of this strategy in a large animal model for future clinical applications, as well as further developing a gene therapy strategy for hypertensive heart disease using other therapeutic genes.
Significance to patient care
Dr. Ikeda and his colleagues are developing novel gene and cell therapy technologies for diabetes, hypertension and hypertensive heart disease. This technology could lead to novel gene and stem cell therapy for patients with these diseases, whose therapeutic options are limited.