, Volume 53, Issue 8, pp 1690-1699

Human islet cell implants in a nude rat model of diabetes survive better in omentum than in liver with a positive influence of beta cell number and purity

Abstract

Aims/hypothesis

Intraportal human islet cell grafts do not consistently and sustainably induce insulin-independency in type 1 diabetic patients. The reasons for losses in donor cells are difficult to assess in patients. This study in streptozotocin-diabetic nude rats examines whether outcome is better in an extra-hepatic site such as omentum.

Methods

Intraportal and omental implants of human islet cell grafts with the same beta cell number were followed for function and cellular composition over 5 weeks. Their outcome was also compared with that of rat islet cell grafts with similar beta cell numbers but higher purity.

Results

While all intraportal recipients of rat islet cell grafts were normoglycaemic until post-transplant (PT) week 5, none was with human islet cell grafts; loss of human implants was associated with early infiltration of natural killer and CD45R-positive cells. Human islet cell implants in omentum achieved plasma human C-peptide positivity and normoglycaemia in, respectively, nine of 13 and five of 13 recipients until PT week 5; failures were not associated with inflammatory infiltrates but with lower beta cell numbers and purity of the grafts. Observations in human and rat islet cell implants in the omentum suggest that a delayed revascularisation can interfere with their metabolic outcome. Irrespective of normalisation, human omental implants presented beta cell aggregates adjacent to alpha cells and duct cells.

Conclusions/interpretation

In nude rats, human islet cell implants survive better in omentum than in liver, with positive influences of the number and purity of implanted beta cells. These observations can guide studies in patients.

D. Jacobs-Tulleneers-Thevissen and K. Bartholomeus contributed equally to this study.