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Transpl Int ; 35: 10697, 2022.
Article in English | MEDLINE | ID: mdl-36685665

ABSTRACT

Neonatal porcine islet-like cell clusters (NPICCs) are a promising source for islet cell transplantation. Excellent islet quality is important to achieve a cure for type 1 diabetes. We investigated formation of cell clusters from dispersed NPICCs on microwell cell culture plates, evaluated the composition of re-aggregated porcine islets (REPIs) and compared in vivo function by transplantation into diabetic NOD-SCID IL2rγ-/- (NSG) mice with native NPICCs. Dissociation of NPICCs into single cells and re-aggregation resulted in the formation of uniform REPI clusters. A higher prevalence of normoglycemia was observed in diabetic NSG mice after transplantation with a limited number (n = 1500) of REPIs (85.7%) versus NPICCs (n = 1500) (33.3%) (p < 0.05). Transplanted REPIs and NPICCs displayed a similar architecture of endocrine and endothelial cells. Intraperitoneal glucose tolerance tests revealed an improved beta cell function after transplantation of 1500 REPIs (AUC glucose 0-120 min 6260 ± 305.3) as compared to transplantation of 3000 native NPICCs (AUC glucose 0-120 min 8073 ± 536.2) (p < 0.01). Re-aggregation of single cells from dissociated NPICCs generates cell clusters with excellent functionality and improved in vivo function as compared to native NPICCs.


Subject(s)
Diabetes Mellitus, Experimental , Islets of Langerhans Transplantation , Islets of Langerhans , Swine , Animals , Mice , Insulin/metabolism , Endothelial Cells , Diabetes Mellitus, Experimental/surgery , Mice, Inbred NOD , Mice, SCID , Islets of Langerhans Transplantation/methods , Glucose/metabolism , Transplantation, Heterologous/methods , Blood Glucose
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