Embryonic stem cell (ESC) differentiation is a potentially powerful approach for generating a renewable source of cells for regenerative medicine. During embryonic development, the inner cell mass (ICM) from which ESCs are derived, differentiate into specific lineages based on a series of temporally and spatially regulated signals. However, the directed differentiation of ESCs in tissue culture typically lacks such tight control and homogenous environments. In most protocols, cell aggregate intermediates called embryoid bodies (EBs) are generated. EBs recapitulate many features of ICM cells during embryonic development and give rise to a wide spectrum of cell types. However, the resulting EBs are typically heterogeneous in size and shape and lack proper temporal and spatial signaling. These variations could be a potential source of heterogeneity in differentiation and prevent uniform and directed cellular differentiation. The goal of this project is 1) to develop and characterize a microfabricated platform to control the homogeneity, size and shape of EBs and 2) to analyze the spatial distribution and frequency of differentiation of definitive and primitive (visceral) endoderm cells as a function of EB size in suspension cultures and within the microfabricated platform. In this project we will develop methods of controlling the homogeneity and differentiation of mouse embryonic stem cells during their first stages of differentiation. This analysis may be useful in directed differentiation of embryonic stem cells for generating therapeutically viable cells. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB007249-02
Application #
7425422
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Hunziker, Rosemarie
Project Start
2007-06-01
Project End
2009-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
2
Fiscal Year
2008
Total Cost
$214,375
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Gaharwar, Akhilesh K; Mihaila, Silvia M; Swami, Archana et al. (2013) Bioactive silicate nanoplatelets for osteogenic differentiation of human mesenchymal stem cells. Adv Mater 25:3329-36
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