个人简介

B.Sc. (Bachelor of Science) Ph.D. (Doctor of Philosophy)

研究领域

Molecular and Development Genetics

1) Pluripotent Stem Cells. We are developing methods for expanding mouse and human pluripotent stem cells (i.e. embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) as aggregates in stirred suspension bioreactors. Bioreactors offer numerous advantages over conventional static culture systems, which lack control and have low cell yields. Bioreactors can be controlled; physiological levels of key parameters can be maintained, and large amounts of cells/tissue can be grown in a short time. Human intervention is minimized, so there is little batch variability. This makes bioreactors an essential step in the application of stem cells. Having demonstrated that the quality of bioreactor expanded cells was equal if not superior to conventional static expansion methods we next explored our ability to differentiate mouse ESCs into different tissue types in the bioreactor. In sharp contrast to static culture, where cell differentiation occurred efficiently, we observed that many cells remained pluripotent in the suspension culture environment and causing them to be refractory to tissue differentiation. Using the mouse model system, we recently demonstrated that in the bioreactor iPSCs form 1000-fold more efficiently, and in half-time compared to static culture. The method is so efficient that we have begun to remove genes from the reprogramming process. Our current research is investigating how fluid shear promotes cellular reprogramming via mechanotransduction. 2) Osteoblast and Chondrocyte Differentiation. We are developing new methods for differentiating mouse and human pluripotent stem cells (PSCs) into osteoblasts and chondrocytes and transplanting them into animal injury models. When cells are affixed to the bottom of micro-drop cultures and treated directly with differentiation factors, some cells undergo apoptosis while others form small chondrocyte or osteoblast fated aggregates in suspension. We have also developed methods to differentiate ESCs within collagen gels. These constructs are sufficient to induce osteoblast formation in the absence of any growth factors: ESCs are simply removed from pluripotency maintenance factors, suspended in collagen gels and cultured for 15 days whereupon they form osteoblasts or chondrocytes in vitro. We have developed a mouse burr-hole fracture model in the proximal tibia, one that is stable and has a known geometry. Osteoblast differentiations derived of male PSCs incorporate into female bone based on Y-chromosome in situ hybridization histochemistry, uCT, and magnetic resonance imaging. Cartilage differentiations are able to form bone when transplanted into animals via a process resembling endochondral ossification.

近期论文

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Zhang BT, Krawetz R, and Rancourt DE (2013) Will the Real Human Embryonic Stem Cell Please Stand Up? Bioessays 35: 632-8. Yamashita A, Liu S, Woltjen K, Thomas B, Meng G, Hotta A, Takahashi K, Ellis J, Yamanaka S, and Rancourt DE. (2013) Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells. Sci Rep 3, Article number: 1978 doi:10.1038/srep01978 Shafa M, Sjonnesen K, Yamashita A, Liu S, Michalak M, Kallos MS and Rancourt DE (2012) Expansion and long term maintenance of induced pluripotent stem cells in stirred suspension bioreactors. J Tiss Eng Reg Med 6: 462-72. Shafa M, Day B, Yamashita A, Meng G, Liu S, Krawetz R and Rancourt DE (2012) Derivation of iPS Cells in Stirred Suspension Bioreactors. Nat Meth 9: 465-466. Krawetz R, Taiani J, Wu YE, Liu S, Meng G, Matyas J, and Rancourt D (2012) Collagen I scaffolds cross-linked with beta-glycerol phosphate induce osteogenic differentiation of embryonic stem cells in vitro and regulate their tumorigenic potential in vivo. Tiss Eng Part A. 18: 1014-1024. Meng G, Liu S, and Rancourt DE (2012) Synergistic effect of medium, matrix and exogenous factors on the adhesion and growth of human pluripotent stem cells under defined, xeno-free conditions. Stem Cells Dev 21: 2036-48.