Histologic differentiation of human fetal pancreatic explants transplanted into nude mice

The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the tissue being cultured in vitro before implantation. These implants coalesced and grew. They were removed at intervals up to 37 wk later and showed selective differentiation of endocrine tissue that normally occurs in the fetus and neonate, with formation of bipolar, mantle, and mature islets. There was growth of this endocrine tissue with significantly more islets than in the freshly stained fetal pancreas assuming an average dimension larger than 150 micron, which is the reported mean diameter of a neonatal islet. Duct and fibrous tissue remained viable, but there was no definitive acinar tissue seen. The pancreata uncultured before implantation reached a larger size than that attained by those implants cultured before being transplanted, the difference probably being the amount of ductular and mesenchymal tissue still present. Of those glands cultured before transplantation, the longer the period of culture, the smaller the size the implants reached. Culture beyond 3 wk in vitro made it difficult to macroscopically locate the implant. These data show that, in human fetal pancreas removed from its usual environment, both selective differentiation of the endocrine component and growth of the islets can occur.