Induction of endocrine differentiation in rodent ES or progenitor cells has been attempted with varying results. Using mES cells, Lumelsky and colleagues have been able to induce insulin-containing cells using an experimental strategy of stepwise selection through changes in culture conditions (43). The levels of insulin may be increased by using growth inhibitors such as phosphatidylinositol 3-kinase inhibitors (44). However, a recent report questions whether the insulin is actually produced by the stem cells or instead passively transferred from the high insulin content of the medium (45). Soria and his group have obtained an insulin-secreting cell clone from undifferentiated mES cells using a cell trap model to select p-cell precursors, which were subsequently able to secrete insulin in response to glucose in vitro and in vivo (46). After growth and differentiation in nonselective media containing serum, murine ES cells spontaneously differentiated into cells individually expressing each of the four major islet hormones in a study recently reported by Kahan and colleagues.
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