第２７回　生命医科学セミナー（Biomedical Science Seminar）

演題：The ROCK inhibitor Y-27632 increases passaging efficiency of Pluripotent Stem Cells; but how, and at what cost?

演者：Dr. Derrick E. Rancourt

所属：Faculty of Medicine, The University of Calgary, Canada

日時：平成２２年１０月１４日（木）　１８：００～１９：００

場所：病院地区総合研究棟、１階１０１講義室

［セミナー内容の紹介］

Pluripotent stem cells (PSCs) have great potential for studying early human embryonic development and are currently being exploited for clinical cell therapies.  Roadblocks presently exist for using PSCs to their full potential, one being the difficultly associated with passaging, expanding and cryo-preserving cells while maintaining pluripotency and high survival rates.  Recent reports have shown that the Rho kinase (ROCK) inhibitor Y-27632 increases the adhesion and survival of PSCs cells; however, the mechanism behind this is poorly understood.  We have found that Y-27632 treatment of PSCs causes morphological changes by disrupting actin stress fibers, and modifying plasma membrane architecture.  Y-27632-induced cellular morphological changes enhanced cell adhesion and survival, yet did not manifest changes in the expression and distribution of the adhesion-associated molecules E-cadherin, N-cadherin, β1-Integrin, β-catenin, and Vinculin.  To further tease out the mechanism of Y-27632 function in PSCs, we also explored the effects of inhibitors to proteins upstream and downstream of ROCK and found that by inhibition of the Rho-ROCK pathway leads to disruption of the actin cytoskeleton eliminating membrane blebs present during routine culture that would otherwise interfere with the passaging and expansion of PSCs cells.  Although Y-27632 treatment is beneficial for expansion and survival of PSCs, we have observed a loss of differentiation capacity in hES and mouse P19 stem cells with Y-27632 treatment.  These results suggest further study into the role of the Rho-ROCK pathway in PSC biology if these cells are to be targeted towards clinical applications.

　今年度の日本学術振興会外国人研究者招へい事業に採択されて研究討議のために来日されます。多くの方の参加を歓迎致します。（共催：福岡医学会）