Recently, embryonic stem (ES) and induced pluripotent stem (iPS) cells have shown remarkable potential to treat human diseases. Biomaterials are rapidly being developed as powerful artificial microenvironments to study and control stem-cell fate, such as proliferation and differentiation. Our recent advances include biomaterial-based artificial extracellular matrix formed by immobilizing cell-recognizable molecule, growth factors and cytokines. Here, we propose “Cadherin-Matrix Engineering” for new frontier of cell-recognizable biomaterials for construction of “Cell-cooking plate” for ES/iPS cells technology using chimeric proteins of cell adhesion molecules (e.g., E-cadherin, N-cadherin, or VE-cadherin).
Our novel E-cadherin-based engineered extracellular matrix showed fascinating results:
(1) highly homogeneous differentiation of definitive endoderm cells under single-cell level; (2) uniform distribution of growth factors resulted in con differentiation even in lower concentration of free culture due to the absence of serum and feeder
layers; (3) completely defined and xeno- short period of differentiation; (4) highly functional hepatocytes within soluble factors; (5) striking effect of matrix-dependent cell sorting for isolation and enrichment of mature hepatocytes for possible elimination of contaminated and poorly differentiated cells; (6) the unique opportunity for continuous monitoring of cellular behavior in different stages of differentiation.
Taken together, our novel recombinant ECM is advantageous for generating homogeneous population of differentiated cells without any enzymatic stress and cell sorting, suggesting that the improved method of differentiation is highly promising for clinically significant adult cells (hepatocytes, neural cells, cardiomyocytes, pancreatic cells and the likes ). We established a novel biomedical field in applied cadherin biology named as “Cadherin-Matrix Engineering” which can be applied to “Cell-cooking Plate” for ES/iPS and other stem cells in regenerative medicine.
