Lack of Evidence for Recipient Precursor Cells Replenishing beta-Cells in Transplanted Islets

Bone marrow and tissue precursor cells have been postulated to replenish grafts of transplanted islets. Several investigators have reported that bone marrow cells can promote the regeneration of injured islets. In this study, we investigated the potential of recipient-derived precursor cells to form new pancreatic endocrine cells in islet grafts transplanted under the kidney capsule. Mouse insulin promoter (MIP)-green fluorescence protein (GFP) mice, which express GFP only in beta-cells, or beta-actin GFP mice, which express GFP ubiquitously, were used to determine if the recipient-derived cells differentiate into beta-cells or other types of endocrine cells. We transplanted MIP-GFP islets into wild-type mice, wild-type islets into MIP-GFP mice, beta-actin GFP islets into wild-type mice, and wild-type islets into beta-actin GFP mice. beta-Actin GFP bone marrow cells were then injected into wild-type mice to evaluate the potential role of bone marrow stem cells to provide new islet cells to the graft. No beta-cells with green fluorescence were seen in the graft when wildtype islets were transplanted into MIP-GFP mice. When wild-type islets were transplanted into beta-actin GFP mice, no beta-cells with GFP staining could be identified in the grafts. Similarly, no endocrine cells with GFP staining could be identified in the grafts after injection of beta-actin GFP bone marrow cells into wild-type islet-transplanted wild-type mice. This study provides further support for the concept that recipient precursor cells do not produce new beta-cells in grafts of transplanted islets.