Embryonic stem cell (ESC) differentiation is a potentially powerful approach for generating a renewable source of cells for regenerative medicine. It is known that the microenvironment greatly influences ESC differentiation and self-renewal. Most biological studies have aimed in identifying individual molecules and signals. However, it is becoming increasingly accepted that the wide array of signals in the ESC microenvironment interact in a synergistic and antagonistic manner based on their temporal and spatial expression, dosage, and specific combinations. This interplay of microenvironmental factors regulates the ESC fate decisions to proliferate, self-renew, differentiate, and migrate. Despite this complexity, the study of stem cell cues in a systematic manner is technologically challenging, expensive, slow, and labor intensive. Here we propose to develop an enabling technology based on a high-throughput microfluidic system that overcomes many of these challenges. By providing a way of testing combinatorial microenvironments for directing stem cell differentiation, this approach promises to be of great benefit for tissue engineering.
A major limitation in treating cardiac injury is the failure of current therapies to induce myocardium regeneration. However, the source of cardiomyocytes for heart failure treatment remains an unsolved problem. We propose to use state-of-the-art microfabricated high-throughput microfluidic devices for studying growth and directed cardiac specific differentiation from embryonic stem cells.
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