Reversal of Hyperglycemia by Intrasplenic Transplantation of 4-Week-Cultured Allogeneic Mouse Islets

Culture of isolated mouse pancreatic islets in RPMI 1640 for 4 wk with maintenance of specific functions is possible, although a considerable reduction of the number of surviving islets was observed. Culture in medium TC 199 resulted in a lower islet loss, but such islets were functionally less competent. Noncultured C57BL/6J (H-2^b) islets were rapidly rejected when allografted intrasplenically into alloxan-diabetic but nonimmunosuppressed C57BL/KsJ (H-2^d) mice. By contrast, the immunogenicity of C57BL/6J islets cultured for 4 wk at 37°C in RPM1 1640 and an air-carbon dioxide atmosphere was markedly reduced as evidenced by their ability to partly or completely normalize the hyperglycemia of nonimmunosuppressed alloxan-diabetic C57BL/KsJ mice for several weeks. Both intact islets and islets undergoing rejection were found in the spleens. The present data suggest that in vitro culture for 4 wk may reduce the immunogenicity of the islets, although a complete suppression is not achieved.