Pluripotent embryonic stem cells from the rat are capable of producing chimeras.

Embryonic stem cells have been enormously important in the production of targeted mutations in mice used in the study of gene function and biological aspects of disease states. The use of these cells for mouse studies is now wide-spread but the production of animals from similar cell lines derived from other species has not been previously reported. We demonstrate here the derivation of diploid rat embryonic stem cells (RESC-01). RESC-01 cells are SSEA-1 and alkaline phosphatase positive, grow best on primary rat embryonic fibroblasts, and can differentiate extensively in vivo. RESC-01 cells form cystic embryoid bodies capable of rhythmic contractions. Rat blastocysts injected with RESC-01 cells form chimeras. The results indicate that the successful in vitro propagation and chimera production with embryonic stem cells is not limited to the mouse. The long-term culture of rat ES cells will provide an important resource for the study of normal physiology and disease models where rat is the species of choice.

Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue.

The mechanism of action of thyroid hormones on bone is still not clear. At low concentrations, they stimulate bone formation; at high concentrations, they elicit bone resorption in vitro and in vivo. In the present study we investigated the effect of T3 and T4 as well as their active and inactive analogs (TRIAC, SKF L-94901, rT3, and DIT) on the IGF-I and TNF-alpha content in the medium of UMR-106 rat osteoblastic cells and fetal rat limb bones. In the dose-response studies, a biphasic increase in medium IGF-I was observed in both cells and limb bones, with peak stimulatory concentrations of 10(-8) M for T3 and 10(-7) M for T4 in both systems. At higher concentrations, at which thyroid hormones elicit bone resorption, the stimulatory effect diminished and finally was no longer detectable. The active analogs TRIAC and SKF L-94901 also enhanced IGF-I release in UMR-106 cells. The inactive compounds rT3 and DIT failed to increase IGF-I in these cultures. The protein content of the cell culture wells exposed to high concentrations of thyroid hormones was similar to those containing low concentrations, indicating that the decrease in IGF-I content at high doses was not due to toxic effects. This was also confirmed by trypan blue exclusion. Time course studies with UMR-106 cells revealed a significant increase in medium IGF-I after 2 days of incubation. No significant further increase was observed after this up to 5 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)