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Generating Partially Differentiated Stem Cells

Pluripotent embryonic stem cells (ESCs) can differentiate into cell types belonging to all three germ layers, making them an ideal source of cells for regenerative therapy. However, the inability to efficiently differentiate ESCs into specific cell types and the presence of contaminating differentiated cells have presented major obstacles to using these cells in regenerative medicine. One strategy to overcome this problem is use ESCs to produce lineage-specific progenitor stem cells, which differentiate into a limited number of cell types of a particular lineage.

MPC have an increased potential to differentiate into endothelial cells.

This is exactly what Manjiri Manohar Bakre and colleagues did in this Paper of the Week. By activating Wnt3A signaling in mouse or human ES cells, they were able to maintain the cells at a state in which they had taken only the first step toward embryonic differentiation. The cells remained committed to the endo/mesodermal lineages, but lost the ability to go ectodermal. These multipotential "mesendodermal progenitor clones" (MPC) expressed increased levels of meso/endodermal and mesendodermal markers and demonstrated enhanced potential to differentiate along endothelial, cardiac, vascular smooth muscle, and skeletal lineages. Thus, the authors demonstrate that Wnt pathway activation can be utilized to generate lineage-specific progenitors from ESCs, which can be further differentiated into desired organ-specific cells.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 31703-31712

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