Peritoneal dissolved oxygen and function of encapsulated adult porcine islets transplanted in streptozotocin diabetic mice.
adult porcine islets
encapsulation
hypoxia
nuclear magnetic resonance
perfluorocarbon
Journal
Xenotransplantation
ISSN: 1399-3089
Titre abrégé: Xenotransplantation
Pays: Denmark
ID NLM: 9438793
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
06
12
2020
received:
25
10
2020
accepted:
24
12
2020
pubmed:
2
2
2021
medline:
18
9
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
Alginate-encapsulated islet xenografts have restored normoglycemia in diabetic animals for various periods of time. Plausible mechanisms of graft failure in vivo include immune rejection and hypoxia. We sought to understand the effects of encapsulated adult porcine islet (API) dosage on the peritoneal dissolved oxygen (DO) level in correlation to the achieved glycemic regulation in diabetic mice. Adult porcine islets encapsulated in barium alginate were transplanted intraperitoneally in streptozotocin diabetic BALB/c mice at 6000 and 4000 islet equivalents (IEQ) and in normal mice at 500 IEQ; APIs encapsulated in calcium alginate were transplanted at 6000 IEQ in diabetic mice. In all cases, cell-free barium alginate capsules containing a perfluorocarbon emulsion were co-implanted for DO measurements using Both barium and calcium alginate-encapsulated APIs at 6000 IEQ reversed diabetes until day 60; barium alginate-encapsulated APIs at 4000 IEQ also reversed diabetes but with a higher failure rate. Transplanted APIs significantly reduced the peritoneal DO, approximately in a dose-dependent manner. The number of viable islets and the insulin content per capsule decreased over time. Capsules retrieved from normoglycemic mice exhibited minimal host cell adherence. Transplantation of encapsulated APIs can reduce peritoneal DO to severely hypoxic levels. Although normoglycemia could be maintained within the study period, the DO levels suggest that hypoxia is a factor contributing to loss of islet viability and insulin secretion with time in mice.
Sections du résumé
BACKGROUND
Alginate-encapsulated islet xenografts have restored normoglycemia in diabetic animals for various periods of time. Plausible mechanisms of graft failure in vivo include immune rejection and hypoxia. We sought to understand the effects of encapsulated adult porcine islet (API) dosage on the peritoneal dissolved oxygen (DO) level in correlation to the achieved glycemic regulation in diabetic mice.
METHODS
Adult porcine islets encapsulated in barium alginate were transplanted intraperitoneally in streptozotocin diabetic BALB/c mice at 6000 and 4000 islet equivalents (IEQ) and in normal mice at 500 IEQ; APIs encapsulated in calcium alginate were transplanted at 6000 IEQ in diabetic mice. In all cases, cell-free barium alginate capsules containing a perfluorocarbon emulsion were co-implanted for DO measurements using
RESULTS
Both barium and calcium alginate-encapsulated APIs at 6000 IEQ reversed diabetes until day 60; barium alginate-encapsulated APIs at 4000 IEQ also reversed diabetes but with a higher failure rate. Transplanted APIs significantly reduced the peritoneal DO, approximately in a dose-dependent manner. The number of viable islets and the insulin content per capsule decreased over time. Capsules retrieved from normoglycemic mice exhibited minimal host cell adherence.
CONCLUSIONS
Transplantation of encapsulated APIs can reduce peritoneal DO to severely hypoxic levels. Although normoglycemia could be maintained within the study period, the DO levels suggest that hypoxia is a factor contributing to loss of islet viability and insulin secretion with time in mice.
Substances chimiques
Alginates
0
Streptozocin
5W494URQ81
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12673Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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