Dept. of Cell Growth and Differentiation
Yoshinori Yoshida (Associate Professor)
Yoshinori Yoshida M.D., Ph.D.
Currently, our lab is using iPS cells to study cardiomyocytes and blood cells with application towards regenerative medicine, drug discovery, and disease modeling. If you are interested, please contact us.
1. Development of myocardial regenerative medicine
Regenerative medicine is critical for patients with currently few treatment options. We are using iPS cells to seek new therapies for this purpose.
2. Disease-specific iPS cells
iPS cells are invaluable for disease models, as they can be designed to recapitulate disease phenotypes in vitro. We use iPS cells to study cardiac diseases (e.g., cardiomyopathies) and hematopoietic disorders (e.g., myelodysplastic syndrome). Furthermore, we use gene editing technology, such as TALENs and CRISPR/Cas9, to modify iPS cells from diseased patients. We then differentiate the edited and unedited iPS patient cells into the cell type of interest and compare the phenotypes. Our laboratory aims to analyze disease mechanisms and develop therapeutic drugs using iPS cells established from the cells of patients with cardiac diseases (cardiomyopathy, cardiac arrhythmias, etc.) and hematological diseases (myelodysplastic syndrome, leukemia, etc.).
3. Cardiomyocytes and blood cells for clinical application
The differentiation of ES/iPS cells to cardiomyocytes has extraordinary potential for new treatments against related diseases. We are investigating differentiation protocols, sorting methods, and transplantation techniques to innovate new therapies. ES/iPS cells also provide an attractive model for drug discovery and toxicity assays. However, cardiomyocytes describe various subtypes, including pacemaker, atrial, and ventricular cells. Each subtype has its role in the function and disease of the heart. Another factor besides the subtype is the maturity of the cardiomyocytes. Therefore, we investigate protocols that differentiate ES/iPS cells into the proper subtype and maturity to study related diseases and novel therapies.
Blood cells and their progenitors produced from ES/iPS cells tend to show poor engraftment when transplanted into mice. It is believed that the maturation of the cells is one reason. Therefore, we are developing differentiation protocols that can control the maturity of blood cells.
4. Investigation into mechanisms determining the differentiation capacity of ES/iPS cells
ES/iPS cell clones show variable differentiation capacity to different somatic cell types. We are investigating the mechanisms that govern these differences by comparing the behavior of the cell lines during differentiation into cardiomyocytes and hematopoietic cells. The goal of this project is to establish iPS cell clones suitable for clinical applications.
Cardiomyocytes derived from human iPS cells
(Green: cardiac isoform of Troponin T, Blue: DAPI)
|Cardiomyocytes derived from human iPS cells provide a transplant for myocardial infarction mouse (Yellow)
|Hematopoietic cells derived from human iPS cells