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Human islet function following 20 years of cryogenic biobanking.

Authors :
Manning Fox JE
Lyon J
Dai XQ
Wright RC
Hayward J
van de Bunt M
Kin T
Shapiro AM
McCarthy MI
Gloyn AL
Ungrin MD
Lakey JR
Kneteman NM
Warnock GL
Korbutt GS
Rajotte RV
MacDonald PE
Source :
Diabetologia [Diabetologia] 2015 Jul; Vol. 58 (7), pp. 1503-12. Date of Electronic Publication: 2015 May 01.
Publication Year :
2015

Abstract

Aims/hypothesis: There are potential advantages to the low-temperature (-196 °C) banking of isolated islets, including the maintenance of viable islets for future research. We therefore assessed the in vitro and in vivo function of islets cryopreserved for nearly 20 years.<br />Methods: Human islets were cryopreserved from 1991 to 2001 and thawed between 2012 and 2014. These were characterised by immunostaining, patch-clamp electrophysiology, insulin secretion, transcriptome analysis and transplantation into a streptozotocin (STZ)-induced mouse model of diabetes.<br />Results: The cryopreservation time was 17.6 ± 0.4 years (n = 43). The thawed islets stained positive with dithizone, contained insulin-positive and glucagon-positive cells, and displayed levels of apoptosis and transcriptome profiles similar to those of freshly isolated islets, although their insulin content was lower. The cryopreserved beta cells possessed ion channels and exocytotic responses identical to those of freshly isolated beta cells. Cells from a subset of five donors demonstrated similar perifusion insulin secretion profiles pre- and post-cryopreservation. The transplantation of cryopreserved islets into the diabetic mice improved their glucose tolerance but did not completely normalise their blood glucose levels. Circulating human insulin and insulin-positive grafts were detectable at 10 weeks post-transplantation.<br />Conclusions/interpretation: We have demonstrated the potential for long-term banking of human islets for research, which could enable the use of tissue from a large number of donors with future technologies to gain new insight into diabetes.

Details

Language :
English
ISSN :
1432-0428
Volume :
58
Issue :
7
Database :
MEDLINE
Journal :
Diabetologia
Publication Type :
Academic Journal
Accession number :
25930156
Full Text :
https://doi.org/10.1007/s00125-015-3598-4