title: Research-Focused Isolation of Human Islets From Donors With and Without Diabetes at the Alberta Diabetes Institute IsletCore.
abstract: Recent years have seen an increased focus on human islet biology, and exciting findings in the stem cell and genomic arenas highlight the need to define the key features of mature human islets and β-cells. Donor and organ procurement parameters impact human islet yield, although for research purposes islet yield may be secondary in importance to islet function. We examined the feasibility of a research-only human islet isolation, distribution, and biobanking program and whether key criteria such as cold ischemia time (CIT) and metabolic status may be relaxed and still allow successful research-focused isolations, including from donors with type 1 diabetes and type 2 diabetes. Through 142 isolations over approximately 5 years, we confirm that CIT and glycated hemoglobin each have a weak negative impacts on isolation purity and yield, and extending CIT beyond the typical clinical isolation cutoff of 12 hours (to ≥ 18 h) had only a modest impact on islet function. Age and glycated hemoglobin/type 2 diabetes status negatively impacted secretory function; however, these and other biological (sex, body mass index) and procurement/isolation variables (CIT, time in culture) appear to make only a small contribution to the heterogeneity of human islet function. This work demonstrates the feasibility of extending acceptable CIT for research-focused human islet isolation and highlights the biological variation in function of human islets from donors with and without diabetes.
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: James
authors.initials: J
authors.lastname: Lyon
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Jocelyn E
authors.initials: JE
authors.lastname: Manning Fox
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Aliya F
authors.initials: AF
authors.lastname: Spigelman
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Ryekjang
authors.initials: R
authors.lastname: Kim
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Nancy
authors.initials: N
authors.lastname: Smith
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Doug
authors.initials: D
authors.lastname: O'Gorman
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kin
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Raymond V
authors.initials: RV
authors.lastname: Rajotte
authors.affiliation: Alberta Diabetes Institute IsletCore (J.L., J.E.M.F., P.E.M.) and Departments of Pharmacology (J.E.M.F., A.F.S., R.K., N.S., P.E.M.) and Surgery (D.O., T.K., A.M.J.S., R.V.R.), University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: MacDonald
mesh_terms: D000328:Adult; D000416:Alberta; D018070:Biological Specimen Banks / Q000458:organization & administration; D002469:Cell Separation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000379:methods*