Influence of Donor Age on Mouse Islet Characteristics and Transplantation

Abstract

Old donor age has been considered as a risk factor and relative contraindication for transplantation. This study was designed to investigate the influence of donor age on islet characteristics and transplantation. Islets isolated from 8 (I-A)-, 32 (I-B)-, or 64 (I-C)-week-old C57BL/6 mice were studied for number, size, insulin content, and secretion. After syngeneically transplanting 300 islets under the kidney capsule of strep-tozotocin-diabetic mice (R-A, R-B, and R-C, respectively), we measured recipients' metabolic parameters as well as the β-cell mass and insulin content of the graft. Eight-week-old donors had better glucose tolerance than 32- and 64-week-old donors. However, 64-week-old donors had more pancreatic insulin content than 8- and 32-week-old donors. I-B and I-C were greater in number, larger in size, and higher in insulin content than I-A. But perifusion study showed I-C secreted less insulin, albeit with a similar stimulation index compared with that of I-A and I-B. After transplantation, the fall of blood glucose in R-C was faster than that in R-A and R-B. At 12 weeks, the recipients' blood glucose, body weight, HbA1c, and the β-cell mass and insulin content of the graft were comparable in all groups. However, R-C had better glucose tolerance than R-A. During follow-up, R-A and R-B maintained lifelong normoglycemia and their glucose tolerance did not deteriorate. These data indicate that islets isolated from donors with different ages have different characteristics and effects on transplantation. The islets isolated from aged donors are functioning well and can be a potential source for transplantation; however, because we transplanted a large islet mass from the aged donors, the role of the islet dose needs to be further clarified.