Influence of donor age on mouse islet characteristics and transplantation

Old donor age has been considered as a risk factor and relative contraindic ation for transplantation. This study was designed to investigate the influ ence of donor age on islet characteristics and transplantation. Islets isol ated from 8 (I-A)-, 32 (I-B)-, or 64 (I-C)-week-old C57BL/6 mice were studi ed for number, size, insulin content, and secretion. After syngeneically tr ansplanting 300 islets under the kidney capsule of streptozotocin-diabetic mice (R-A, R-B, and R-C, respectively), we measured recipients' metabolic p arameters as well as the P-cell mass and insulin content of the graft. Eigh t-week-old donors had better glucose tolerance than 32- and 64-week-old don ors. 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 siz e, and higher in insulin content than I-A. But perifusion study showed I-C secreted less insulin, albeit with a similar stimulation index compared wit h 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, HbA(lc), and the beta -cell mass and insulin content of the graft were comparable in all groups. However, R-C had better glucos e tolerance than R-A. During follow-up, R-A and R-B maintained lifelong nor moglycemia and their glucose tolerance did not deteriorate. These data indi cate that islets isolated from donors with different ages have different ch aracteristics and effects on transplantation. The islets isolated from aged donors are functioning well and can be a potential source for transplantat ion; however, because we transplanted a large islet mass from the aged dono rs, the role of the islet dose needs to be further clarified.