Formation of amyloid in encapsulated human pancreatic and human stem cell-generated beta cell implants.
animal models: murine
clinical research/practice
diabetes: new onset/posttransplant
encapsulation
endocrinology/diabetology
islet transplantation
islets of Langerhans
pathology/histopathology
stem cells
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
16
10
2020
received:
29
06
2020
accepted:
02
11
2020
pubmed:
19
11
2020
medline:
29
6
2021
entrez:
18
11
2020
Statut:
ppublish
Résumé
Detection of amyloid in intraportal islet implants of type 1 diabetes patients has been proposed as cause in their functional decline. The present study uses cultured adult human islets devoid of amyloid to examine conditions of its formation. After intraportal injection in patients, amyloid deposits <15 µm diameter were identified in 5%-12% of beta cell containing aggregates, 3-76 months posttransplant. Such deposits also formed in glucose-controlling islet implants in the kidney of diabetic mice but not in failing implants. Alginate-encapsulated islets formed amyloid during culture when functional, and in all intraperitoneal implants that corrected diabetes in mice, exhibiting larger sizes than in functioning nonencapsulated implants. After intraperitoneal injection in a patient, retrieved single capsules presented amyloid near living beta cells, whereas no amyloid occurred in clustered capsules with dead cells. Amyloid was also demonstrated in functional human stem cell-generated beta cell implants in subcutaneous devices of mice. Deposits up to 35 µm diameter were localized in beta cell-enriched regions and related to an elevated IAPP over insulin ratio in the newly generated beta cells. Amyloid in device-encapsulated human stem cell-generated beta cell implants marks the formation of a functional beta cell mass but also an imbalance between its activated state and its microenvironment.
Identifiants
pubmed: 33206461
doi: 10.1111/ajt.16398
pii: S1600-6135(22)08585-9
doi:
Substances chimiques
Amyloid
0
Islet Amyloid Polypeptide
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2090-2099Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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