Cell Transplantation (Sep 2015)

Human Pancreatic Islets Isolated from Donors with Elevated HbA1c Levels: Islet Yield and Graft Efficacy

  • Meirigeng Qi,
  • Brian McFadden,
  • Luis Valiente,
  • Keiko Omori,
  • Shiela Bilbao,
  • Jemily Juan,
  • Jeffrey Rawson,
  • Alina R. Oancea,
  • Stephen Scott,
  • Indu Nair,
  • Kevin Ferreri,
  • Yoko Mullen,
  • Donald Dafoe,
  • Mohamed Ei-Shahawy,
  • Fouad Kandeel,
  • Ismail H. Al-Abdullah

DOI
https://doi.org/10.3727/096368914X683548
Journal volume & issue
Vol. 24

Abstract

Read online

The aim of this study was to investigate the effects of elevated donor HbA1c levels (type 2 diabetes, T2D) on the islet yield and functionality postisolation. In this retrospective analysis, donors for islet isolations were classified into two groups: T2D group (HbA1c ≥ 6.5%, n = 18) and normal group (HbA1c < 6.5%, n = 308). Optimum pancreas digestion time (switch time) was significantly higher in the T2D group compared to the normal group (13.7 ± 1.2 vs. 11.7 ± 0.1 min, respectively, p = 0.005). Islet yields were significantly lower in the T2D group compared to the control (T2D vs. control): islet equivalent (IEQ)/g (prepurification 2,318 ± 195 vs. 3,713 ± 114, p = 0.003; postpurification 1,735 ± 175 vs. 2,663 ± 89, p = 0.013) and islet particle number (IPN)/g (prepurification, 2,519 ± 336 vs. 4,433 ± 143, p = 0.001; postpurification, 1,760 ± 229 vs. 2,715 ± 85, p = 0.007). Islets from T2D pancreata had significantly lower viability (T2D vs. control: 91.9 ± 1.6 vs. 94.4 ± 0.3%, p = 0.004) and decreased oxygen consumption rate (DOCR) (T2D vs. control: 0.09 ± 0.01 and 0.21 ± 0.03 nmol O 2 100 islets −1 min −1 , p = 0.049). The islets isolated from T2D donor pancreata reversed diabetes in NOD-SCID mice in 9% (2/22) compared to islets from control donor pancreata, which reversed diabetes in 67% (175/260, p < 0.001). In conclusion, this study demonstrates that elevated HbA1c (≥6.5%) is associated with impairment of islet function and lower islet yield; however, these islets could not be suitable for clinical applications.