title: Supplements in human islet culture: human serum albumin is inferior to fetal bovine serum.
abstract: Culture of human islets before clinical transplantation or distribution for research purposes is standard practice. At the time the Edmonton protocol was introduced, clinical islet manufacturing did not include culture, and human serum albumin (HSA), instead of fetal bovine serum (FBS),  was used during other steps of the process to avoid the introduction of xenogeneic material. When culture was subsequently introduced, HSA was also used for medium supplementation instead of FBS, which was typically used for research islet culture. The use of HSA as culture supplement was  not evaluated before this implementation. We performed a retrospective analysis of 103 high-purity islet preparations (76 research preparations, all with FBS culture supplementation, and 27 clinical preparations, all with HSA supplementation) for oxygen consumption rate per DNA content (OCR/DNA;  a measure of viability) and diabetes reversal rate in diabetic nude mice (a measure of potency). After 2-day culture, research preparations exhibited an average OCR/DNA 51% higher (p < 0.001) and an average diabetes reversal rate 54% higher (p < 0.05) than clinical preparations,  despite 87% of the research islet preparations having been derived from research-grade pancreata that are considered of lower quality. In a prospective paired study on islets from eight research preparations, OCR/DNA was, on average, 27% higher with FBS supplementation than that with HSA supplementation  (p < 0.05). We conclude that the quality of clinical islet preparations can be improved when culture is performed in media supplemented with serum instead of albumin.
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Avgoustiniatos
authors.forename: William E
authors.initials: WE
authors.lastname: Scott
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suszynski
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Nelson
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Rozak
authors.forename: Kate R
authors.initials: KR
authors.lastname: Mueller
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ansite
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Fraga
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Friberg
authors.forename: Gina M
authors.initials: GM
authors.lastname: Wildey
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Connor A
authors.initials: CA
authors.lastname: Lyons
authors.forename: David E R
authors.initials: DE
authors.lastname: Sutherland
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Hering
authors.forename: Klearchos K
authors.initials: KK
authors.lastname: Papas
mesh_terms: D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000401:mortality / Q000601:surgery; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D016381:Islets of Langerhans Transplantation; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D010101:Oxygen Consumption; D012189:Retrospective Studies; D044967:Serum; D012709:Serum Albumin / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D003470:Culture Media; D012709:Serum Albumin