Graduate School of Medicine ＞ Human Science
＞Histology and Embryology

Professor: Katsunori Sasaki
Associate Professor: Kohei Johkura
Assistant Professor: Daihachiro Tomotsune, Fengming Yue

Summary of Activity
The ultimate goal of our research is to develop functional tissues or organs that can replace damaged organs. The research integrates the disciplines of developmental biology, bioengineering and human anatomy. Induction and generation of differentiated cells from stem cells such as human embryonic stem (ES) cells, and induced pluripotent stem (iPS) cells could represent an advantageous source of cells for the cell replacement therapy. We have developed protocols for the differentiation of human or mouse ES cells into a variety of cell types including cardiomyocytes, hepatocytes and pancreatic cells and tried to purify and organize them into tissues.


Research Projects
The current research projects are as follows.
* Development of an efficient cryopreservation method for human ES cells
* Refinement of the culture system for maintaining the undifferentiated state of ES cells by using various conditions including xylose supply
* Establishment of effective differentiation method of ES and iPS cells into cardiomyocytes, hepatocytes and pancreatic cells
* Transgenic approach for directed differentiation of ES cells into desired cell types.
*Differentiation of ES or iPS cells into retinal cells induced by ES or iPS cell-derived pigmented cells
*Transdifferentiation of adult glia cells into dopaminergic neurons
* Transdifferentiation of the hepatic cells to the pancreatic cells using small molecules
* Dedifferentiation and reactivation of adult primary hepatocytes into proliferative state by virus-mediated gene transfer
* Embryological analysis of differentiating ES cells (developmental biology of embryoid body)
* Study on the mechanism of Wolffian duct maintenance toward application to kidney tissue regeneration

References
  1. Yue F, Johkura K, Shirasawa S, Yokoyama T, Inoue Y, Tomotsune D, Sasaki K, (2010) Differentiation of primate ES cells into retinal cells induced by ES cell-derived pigmented cells. Biochem Biophys Res Commun. 394: 877-883.

  2. Mae S, Shirasawa S, Yoshie S, Sato F, Kanoh Y, Ichikawa H, Yokoyama T, Yue F, Tomotsune D, Sasaki K, (2010) Combination of small molecules enhances differentiation of mouse embryonic stem cells into intermediate mesoderm through BMP7-positive cells. Biochem Biophys Res Commun. 393: 877-882.

  3. Yoshie S, Shirasawa S,Yokoyama T, Kanoh Y, Takei S, Mizuguchi M, Matsumoto K, Tomotsune D, Sasaki K, (2010) Lanford medium induces high quality hepatic lineage cell differentiation directly from mouse embryonic stem cell-derived mesendoderm. Biochem Biophys Res Commun. 391: 1477-1482.

  4. Sasaki K, Ichikawa H, Takei S, No H, Tomotsune D, Kano Y, Yokoyama T, Shirasawa S, Mogi A, Yoshie S, Sasaki S, Yamada S, Matsumoto K, Mizoguchi M, Yue F, Tanaka Y, (2009) Hepatocyte differntiation from human ES cells using the simple embryoid body formation method and the staged-additional cocktail. TheScientificWorld. 9: 884-890.

  5. Takei S, Ichikawa H, Johkura K, Mogi A, No H, Yoshie S, Tomotsune D, Sasaki K, (2009) Bone morphogenetic protein-4 promotes induction of cardiomyocytes from human embryonic stem cells in serum-based embryoid body development. Am J Physiol Heart Circ Physiol. 296: 1793-1803.

  6. Takashimizu I, Tanaka Y, Yoshie S, Kano Y, Ichikawa H, Cui L, Ogiwara N, Johkura K, Sasaki K, (2009) Localization of Liv2 as an immature hepatocyte marker in EB outgrowth. ScientificWorldJournal. 9: 190-199.

  7. Mogi A, Ichikawa H, Matsumoto C, Tomotsune D, Sasaki S, Yamada S, Sasaki K, (2009) The method of mouse embryoid body establishment affects structure and developmental gene expression. Tissue Cell. 41: 79-84.

  8. Cui L, Johkura K, Takei S, Ogiwra N, Sasaki K, (2007) Structural differentiation, proliferation, and association of human embryonic stem cell-derived cardiomyocytes in vitro and their extracardiac tissues. J Struct Biol 158: 307-317.

  9. Ichikawa H, No H, Takei S, Takashimizu I, Feming Y, Cui L, Ogiwara N, Johkura K,Nishimoto Y, Sasaki K（2007）Cryopreservation of mouse embryoid bodies. Cryobiology 54: 290-293.

  10. Yue F, Cui L, Johkura K, Ogiwara N, Sasaki K, (2006) Induction of midbrain dopaminergic neurons from primate ES cells by co-culture with Sertoli cells Stem Cells, 24: 1695-1706.