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Application of Chimera Protein Matrices for Stem Cell Engineering and Regenerative Medicine

Speaker: Professor - AKAIKE, Toshihiro
When: 15:30, March 28, 2011 ~ 16:30, March 28, 2011
Where: Room 108, Med-X Institute, Xuhui Campus, SJTU

Topic: Application of Chimera Protein Matrices for Stem Cell Engineering and Regenerative Medicine

Recently, the design of biomaterials has been considered to need various nantechnological methods which can regulate based on cell-cell, cell-cytokine, and cell-matrix interactions. For the nano-level regulations of these cell-participating interactions, nano-sized cell recognizing and cell-activating polymers or chimeric proteins are newly engineered and applied to ES/iPS cells, liver cells, and the like. We have been making efforts to design cell-recognizable macromolecules for the cell attachment based on synthetic and gene engineering for these thirty years. ES/iPS cells have a potency to differentiate into multiple cell types in vivo and also in vitro, while the mechanism and regulation system of their properties were still unknown. We tried to design the engineered biomaterials which contain specific ligands and could regulate cell functions, e.g. cell proliferation differentiation, and morphogenesis, and to apply these materials as a adhesive matrices for ES/iPS cell culture. We focused on the cell-cell adhesion proteins "cadherin" and several growth factors such as BMP, Activin and IGF-1 that regulate stem cell functions, and constructed cell-recognizable matrices as a fusion protein with IgG Fc region. Cadherins mediates calcium-dependent homophilic adhesion between same cadherin molecules, and tissue specific expression of cadherin molecules is required for cell sorting and recognition during embryogenesis and for differentiation into specific cell lineages. When cultured on the plates coated with E-cadherin-IgG Fc fusion proteins, murine ES (embryonic stem) cells do not make cell-cell contacts or form colonies, which was quite different from the conventional culture methods on gelatin and other ECM.

The cells on E- cadherin surface retained all ES cell features, and showed a higher proliferative ability, lower dependency on LIF, and higher transfection efficiency, which indicated that this system should enable more efficient culture of ES cells. We also constructed N-cadherin-model matrices and investigated the effect of N-cadherin-mediated cell adhesion on the differentiation of stem cells. P19 and MEB5 embryonal carcinoma cells can differentiate into cardiac cells and neural in vitro depending on the culture condition, and cell-cell interaction has a crucial role in their differentiation. P19 and MEB5 cells showed different responses on the N-cadherin-coated surface depending on the coating concentration of N-cadherin model molecule. These results suggested that cell-recognizable matrix-engineering could be useful for establishment of novel system to clarify stem cell biology in regenerative medicine.

Speaker biography:

  • 1975    Ph.D., Major: Synthetic Chemistry, University of Tokyo
  • 1975~1981  Research Associate, Department of Surgical Science, The Heart
  • Institute of Japan, Tokyo Women's Medical College (Presently "University")
  • 1980~1990  Associate Professor, Department of Material Systems Engineering, Faculty of Technology, Tokyo University of Agriculture and Technology
  • 1989~1995  Project Leader, Kanagawa Academy of Sci & Tech.
  • 1989,1996  Visiting Professor of University of Paris XIII (France)
  • 2000    Visiting Professor of Harbin Medical University (China)
  • 2000~2003  Professor of Shinshu University Graduate School of Medicine
  • 1990~    Present Professor of Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Department of Biomolecular Engineering