Morphology and Function of Cultured Human Fetal Pancreatic Cells Transplanted into Athymic Mice: A Longitudinal Study

Abstract

Islet-like cell clusters generated from human fetal pancreases between 18-24 wk gestation were able to grow and mature both morphologically and functionally after transplantation under the kidney capsule of athymic nude mice. Grafted tissue, predominantly ductal in appearance was unresponsive to glucose 2 wk after grafting. The tissue assumed the trabecular column-like architecture of adult islets by 3 mo, with a concomitant 3-4-fold increase in serum human C-peptide concentration after glucose challenge. Moreover, at that time the surface area of insulin containing cells in the graft increased 20-fold over the starting material. Exocrine components, identified by their characteristic eosinophilic secretory granules were also identified at this time. Transplanted cell clusters were capable of releasing C-peptide for at least 12 mo, when the experiment was terminated. At this time, 1 yr posttransplantation, although the proportion of insulin containing cells in the graft remained unchanged from that measured at 4 mo, a reduction in the magnitude of the C-peptide response to glucose was observed; this finding coincided with a significant mononuclear infiltrate in some areas of the transplanted tissue. In summary, human fetal pancreatic cells grown in tissue culture as cell aggregates, after transplantation under the kidney capsule, remain functionally viable for virtually the life span of immunocompromised rodents. Because of their long-term viability, the use of islet-like cell clusters is a potentially useful method to expand transplantable cells.