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Study · Animal study (in vivo) · mouse · 2021

7 results

Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation.

Yao M, Domogatskaya A, Ågren N, Watanabe M, Tokodai K, Brines M, Cerami A, Ericzon BG, Kumagai-Braesch M, Lundgren T

Cell transplantation1 Jan 2021Cited by 8 (Europe PMC)

PMID34498509 (opens in a new tab)PMCIDPMC8436319 (opens in a new tab)DOI10.1177/09636897211039739 (opens in a new tab)PepBankPUB-34498509
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Summary

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.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In athymic mice given human islets via the portal vein, cibinetide treatment increased human insulin in the livers compared with controls.

    In plain wordsIn mice that received human islets, cibinetide treatment led to more human insulin in the liver than in controls.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    IncreaseHuman insulin in recipient livers
    Study

    mousen: not reported in source

    Human islets transplanted into athymic mice livers via the portal vein
    Comparator
    Controls
    Outcome group
    Islet protection · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    cibinetide treatment showed an increased amount of human insulin in the livers
    2 context sentences
    Summary · context
    Moreover, human islets were transplanted into athymic mice livers via the portal vein with or without perioperative cibinetide treatment.
    Summary · context
    The mice were sacrificed six days following transplantation and the livers were analyzed for human insulin and serum for human C-peptide levels.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In athymic mice given human islets via the portal vein, cibinetide treatment gave higher serum human C-peptide than controls.

    In plain wordsIn mice that received human islets, cibinetide treatment led to higher human C-peptide in the blood than in controls.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    IncreaseSerum human C-peptide
    Study

    mousen: not reported in source

    Human islets transplanted into athymic mice livers via the portal vein
    Comparator
    Controls
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    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.
    2 context sentences
    Summary · context
    Moreover, human islets were transplanted into athymic mice livers via the portal vein with or without perioperative cibinetide treatment.
    Summary · context
    The mice were sacrificed six days following transplantation and the livers were analyzed for human insulin and serum for human C-peptide levels.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In athymic mice given human islets via the portal vein, cibinetide treatment reduced infiltration of pro-inflammatory CD11b+ cells around islet grafts compared with controls.

    In plain wordsIn mice that received human islets, cibinetide treatment led to fewer inflammatory immune cells around the grafts than in controls.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseCD11b+ cell infiltration around islet grafts
    Study

    mousen: not reported in source

    Human islets transplanted into athymic mice livers via the portal vein
    Comparator
    Controls
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    histological examination of the livers showed reduced infiltration of pro-inflammatory CD11b+ cells around islets grafts compared to the controls.
    1 context sentence
    Summary · context
    Histological examination of recipient livers to evaluate islet graft infiltration by CD11b+ cells was performed.
  4. 04LabEx vivo tissueEfficacy outcome

    In a loop system with human islets and ABO compatible blood, cibinetide reduced IBMIR-induced platelet consumption.

    In plain wordsIn lab tests with human islets and blood, cibinetide reduced the loss of platelets caused by the early immune reaction.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseIBMIR-induced platelet consumption
    Study

    humann: not reported in source

    Human islets with ABO compatible blood in heparinized PVC tubing loop
    Comparator
    Control (no cibinetide)
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the PVC loop system, administration of cibinetide reduced the IBMIR-induced platelet consumption.
    1 context sentence
    Summary · context
    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.
  5. 05LabIn vitro (cells)Efficacy outcome

    In human islets cultured with pro-inflammatory cytokines, cibinetide maintained islet ATP levels compared with culture without cibinetide.

    In plain wordsIn cells, cibinetide kept human islets' ATP levels up during exposure to inflammatory signals, compared with no cibinetide.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    IncreaseIslet ATP content
    Study

    humann: not reported in source

    Human islets cultured with pro-inflammatory cytokines
    Comparator
    Cytokines without cibinetide
    Outcome group
    Islet protection · Endocrine and hormones
    Studied dose
    Dose not stated · 18 hoursAs given in this study (human).

    Source sentences

    Summary
    cibinetide maintained human islet ATP levels
    1 context sentence
    Summary · context
    We cultured human islets with pro-inflammatory cytokines for 18 hours with or without cibinetide.
  6. 06LabIn vitro (cells)Efficacy outcome

    In human islets cultured with pro-inflammatory cytokines, cibinetide reduced caspase 3/7 activity compared with culture without cibinetide.

    In plain wordsIn cells, cibinetide lowered a cell-death marker in human islets exposed to inflammatory signals, compared with no cibinetide.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseIslet caspase 3/7 activity
    Study

    humann: not reported in source

    Human islets cultured with pro-inflammatory cytokines
    Comparator
    Cytokines without cibinetide
    Outcome group
    Islet protection · Endocrine and hormones
    Studied dose
    Dose not stated · 18 hoursAs given in this study (human).

    Source sentences

    Summary
    reduced the caspase 3/7 activity during culture with pro-inflammatory cytokines
    1 context sentence
    Summary · context
    We cultured human islets with pro-inflammatory cytokines for 18 hours with or without cibinetide.
  7. 07LabIn vitro (cells)Efficacy outcome

    In human islets cultured with pro-inflammatory cytokines, cibinetide improved insulin secreting capacity compared with culture without cibinetide.

    In plain wordsIn cells, cibinetide improved the insulin-making ability of human islets exposed to inflammatory signals, compared with no cibinetide.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    IncreaseIslet insulin secreting capacity
    Study

    humann: not reported in source

    Human islets cultured with pro-inflammatory cytokines
    Comparator
    Cytokines without cibinetide
    Outcome group
    Glycemic control · Endocrine and hormones
    Studied dose
    Dose not stated · 18 hoursAs given in this study (human).

    Source sentences

    Summary
    improved their insulin secreting capacity.
    2 context sentences
    Summary · context
    We cultured human islets with pro-inflammatory cytokines for 18 hours with or without cibinetide.
    Summary · context
    Dynamic glucose perfusion assay was used to evaluate islet function.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:13 UTC

    First added · source update from Europe PMC

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