Joint Research Chair

Cell Design for Tissue Construction

Basic research for cell differentiation and tissue constuction towards clinical application
  • Use of novel compound KY03-1 to induce iPS cell differentiation to cardiomyocytes for clinical application
  • New cell dfferetiation techniques for domestic and foreign iPS cell lines
  • New cytochemistry and tissue engineering techniques for the transplantation of iPS cell-derived cardiomyocytes
  • Use of Cellnest, a recombinant peptide, for tissue engineering and regenerative medicine

Next generation iPS cell differentiation technology and tissue engineering for regenerative medicine

We have developed a protein-free method that uses small compounds to induce the differentiation of iPS cells to cardiomyocytes for clinical application. We are testing our system on clinical-grade iPS cell lines from both inside and outside Japan and large-scale culture. Using recombinant peptides (RCP) from Fujifilm and new culture technology, we are preparing living tissues from the cardiomyocytes. The differentiated cells and tissues are being used in rat and pig transplant models for the purpose of optimizing the engraftment efficiency and therapeutic effect.

Figure

Heart disease is the leading cause of death in the world. Both drug discovery and regenerative medicine for the disease require the provision of human cardiomyocytes, but functional cardiomyocytes are difficult to produce because of their low proliferation ability. iPS cells offer the potential to prepare functional cardiomyocytes at industrial level in an ethical manner. However, the safety, stability and cost efficiency of the cells remains as issues . We are considering ways to reduce the cost of current differentiation cultures, biological polymers and growth factors for the cardiomyocyte differentiation.

Using a chemical screening, we discovered the compounds KY02111 and KY03-I, which efficiently induce the differentiation of iPS cells to cardiomyocytes [1]. Our differentiation protocol only requires small compounds and amino acids in the culture. The purity of cardiomyocytes is high at more than 90%, and the production efficiencies of cells are remarkably stable. Furthermore, our method has low cost and low risk of virus contamination. It is also compatible with a three-dimensional suspension culture system, making it suitable for large scale production of cardiomyocytes.

Because of its low cost and the high quality cells, we are testing our novel cell differentiation induction method on multiple iPS cell lines and combining it with tissue engineering to develop new regenerative medicine and other cell therapies.

Reference

1. Cell Reports 29; 2 (5): 1448-60, 2012.