Study summary · research use only
Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study used human pancreatic islets in vitro and athymic mice in vivo to examine the erythropoietin analogue cibinetide for intra-portal islet transplantation (PITx). Human islets cultured with cytokines for 18 hours with or without cibinetide were assessed for ATP content, caspase 3/7 activity, and function via glucose perfusion; cibinetide was associated with maintained ATP levels, reduced caspase 3/7 activity, and improved insulin secretion. In a heparinized tubing system mimicking the portal vein with ABO-compatible blood rotated 60 minutes, cibinetide reduced platelet consumption linked to the instant blood mediated inflammatory reaction (IBMIR). In athymic mice receiving human islet transplants via the portal vein, perioperative cibinetide was associated with higher human insulin in livers and serum human C-peptide six days post-transplant, and reduced CD11b-positive cell infiltration around grafts on histology.
Abstract
During intra-portal pancreatic islet transplantation (PITx), innate immune reactions such as the instant blood mediated inflammatory reaction (IBMIR) cause an immediate loss of islets. The non-hematopoietic erythropoietin analogue cibinetide has previously shown islet-protective effects in mouse PITx. Herein, we aimed to confirm cibinetide's efficacy on human islets, and to characterize its effect on IBMIR. We cultured human islets with pro-inflammatory cytokines for 18 hours with or without cibinetide. ATP content and caspase 3/7 activity were measured. Dynamic glucose perfusion assay was used to evaluate islet function. To evaluate cibinetides effect on IBMIR, human islets were incubated in heparinized polyvinyl chloride tubing system with ABO compatible blood and rotated for 60 minutes to mimic the portal vein system. Moreover, human islets were transplanted into athymic mice livers via the portal vein with or without perioperative cibinetide treatment. The mice were sacrificed six days following transplantation and the livers were analyzed for human insulin and serum for human C-peptide levels. Histological examination of recipient livers to evaluate islet graft infiltration by CD11b+ cells was performed. Our results show that cibinetide maintained human islet ATP levels and reduced the caspase 3/7 activity during culture with pro-inflammatory cytokines and improved their insulin secreting capacity. In the PVC loop system, administration of cibinetide reduced the IBMIR-induced platelet consumption. In human islet to athymic mice PITx, cibinetide treatment showed an increased amount of human insulin in the livers and higher serum human C-peptide, while histological examination of the livers showed reduced infiltration of pro-inflammatory CD11b+ cells around islets grafts compared to the controls. In summary, Cibinetide protected isolated human islets in a pro-inflammatory milieu and reduced IBMIR related platelet consumption. It improved engraftment of human islets in athymic mice. The study confirms that cibinetide is a promising agent to be used in clinical PITx.
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