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Study · Animal study (in vivo) · mouse · 2017

9 results

Exendin-4 in combination with adipose-derived stem cells promotes angiogenesis and improves diabetic wound healing.

Seo E, Seo E, Lim JS, Jun JB, Choi W, Hong IS, Jun HS

Journal of translational medicine15 Feb 2017Cited by 78 (Europe PMC)

PMID28202074 (opens in a new tab)PMCIDPMC5311833 (opens in a new tab)DOI10.1186/s12967-017-1145-4 (opens in a new tab)PepBankPUB-28202074
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Summary

BackgroundDiminished wound healing is a major complication of diabetes mellitus and can lead to foot ulcers. However, there are limited therapeutic methods to treat this condition. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, is known to have many beneficial effects on diabetes. In addition, mesenchymal stem cells are known to have wound healing effects. We investigated the effects of Ex-4 in combination with human adipose tissue-derived stem cells (ADSCs) on diabetic wound healing in a diabetic animal model.MethodsDiabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back. One day after wounding, each wound received ADSCs (2.5 × 105 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily. Wound size was monitored and wound histology was examined. Human endothelial cells and keratinocyte cells were used to assess angiogenesis and vascular endothelial growth factor expression in vitro.ResultsTopical administration of Ex-4 or injection of ADSCs resulted in a rapid reduction of wound size in both diabetic and normoglycemic animals compared with vehicle treatment. Histological analysis also showed rapid skin reconstruction in Ex-4-treated or ADSC-injected wounds. A combination of Ex-4 and ADSCs showed a significantly better therapeutic effect over either treatment alone. In vitro angiogenesis assays showed that both Ex-4 and ADSC-conditioned media (CM) treatment improved migration, invasion and proliferation of human endothelial cells. ADSC-CM also increased migration and proliferation of human keratinocytes. In addition, both Ex-4 and ADSC-CM increased the expression of vascular endothelial growth factor. Co-culture with ADSCs increased migration and proliferation of these cells similar to that found after ADSC-CM treatment.ConclusionsWe suggest that Ex-4 itself is effective for the treatment of diabetic skin wounds, and a combination of topical treatment of Ex-4 and injection of ADSCs has a better therapeutic effect. Thus, a combination of Ex-4 and ADSCs might be an effective therapeutic option for the treatment of diabetic wounds, such as foot ulcers.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In diabetic mice, topical Ex-4 reduced wound size more rapidly than vehicle.

    In plain wordsIn diabetic mice, topical Ex-4 reduced wound size more rapidly than vehicle.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseDiabetic wound size
    Study

    mousen: not reported in source

    Diabetic db/db mice
    Comparator
    Vehicle
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    50 μl of 100 nM Ex-4 daily · topicalAs given in this study (mouse).

    Source sentences

    Summary
    Topical administration of Ex-4 or injection of ADSCs resulted in a rapid reduction of wound size in both diabetic and normoglycemic animals compared with vehicle treatment.
    2 context sentences
    Summary · context
    Diabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back.
    Summary · context
    One day after wounding, each wound received ADSCs (2.5 × 105 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In normoglycemic mice, topical Ex-4 reduced wound size more rapidly than vehicle.

    In plain wordsIn normoglycemic mice, topical Ex-4 reduced wound size more rapidly than vehicle.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseNormoglycemic wound size
    Study

    mousen: not reported in source

    Normoglycemic C57BL/6 mice
    Comparator
    Vehicle
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    50 μl of 100 nM Ex-4 daily · topicalAs given in this study (mouse).

    Source sentences

    Summary
    Topical administration of Ex-4 or injection of ADSCs resulted in a rapid reduction of wound size in both diabetic and normoglycemic animals compared with vehicle treatment.
    2 context sentences
    Summary · context
    Diabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back.
    Summary · context
    One day after wounding, each wound received ADSCs (2.5 × 105 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mouse wounds, Ex-4 treatment produced rapid skin reconstruction on histological examination.

    In plain wordsIn mice, Ex-4-treated wounds showed rapid skin reconstruction.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseSkin reconstruction
    Study

    mousen: not reported in source

    Diabetic and normoglycemic mouse skin wounds
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    50 μl of 100 nM Ex-4 daily · topicalAs given in this study (mouse).

    Source sentences

    Summary
    Histological analysis also showed rapid skin reconstruction in Ex-4-treated or ADSC-injected wounds.
    2 context sentences
    Summary · context
    Diabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back.
    Summary · context
    One day after wounding, each wound received ADSCs (2.5 × 105 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mouse wounds, Ex-4 plus ADSCs produced a better therapeutic effect than ADSCs alone.

    In plain wordsIn mice, Ex-4 plus stem cells improved wound treatment results more than stem cells alone.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseCombination therapeutic effect versus ADSCs
    Study

    mousen: not reported in source

    Diabetic and normoglycemic mouse skin wounds
    Comparator
    ADSCs alone
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    50 μl of 100 nM Ex-4 daily · topicalAs given in this study (mouse).

    Source sentences

    Summary
    A combination of Ex-4 and ADSCs showed a significantly better therapeutic effect over either treatment alone.
    2 context sentences
    Summary · context
    Diabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back.
    Summary · context
    One day after wounding, each wound received ADSCs (2.5 × 105 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily.
  5. 05LabIn vitro (cells)Efficacy outcome

    In human endothelial cells, Ex-4 improved migration.

    In plain wordsIn cells, Ex-4 improved human endothelial cell migration.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseEndothelial cell migration
    Study

    humann: not reported in source

    Human endothelial cells
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro angiogenesis assays showed that both Ex-4 and ADSC-conditioned media (CM) treatment improved migration, invasion and proliferation of human endothelial cells.
    1 context sentence
    Summary · context
    Human endothelial cells and keratinocyte cells were used to assess angiogenesis and vascular endothelial growth factor expression in vitro.
  6. 06LabIn vitro (cells)Efficacy outcome

    In human endothelial cells, Ex-4 improved invasion.

    In plain wordsIn cells, Ex-4 improved human endothelial cell invasion.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseEndothelial cell invasion
    Study

    humann: not reported in source

    Human endothelial cells
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro angiogenesis assays showed that both Ex-4 and ADSC-conditioned media (CM) treatment improved migration, invasion and proliferation of human endothelial cells.
    1 context sentence
    Summary · context
    Human endothelial cells and keratinocyte cells were used to assess angiogenesis and vascular endothelial growth factor expression in vitro.
  7. 07LabIn vitro (cells)Efficacy outcome

    In human endothelial cells, Ex-4 improved proliferation.

    In plain wordsIn cells, Ex-4 improved human endothelial cell proliferation.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseEndothelial cell proliferation
    Study

    humann: not reported in source

    Human endothelial cells
    Outcome group
    Wound healing · Skin and wound
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro angiogenesis assays showed that both Ex-4 and ADSC-conditioned media (CM) treatment improved migration, invasion and proliferation of human endothelial cells.
    1 context sentence
    Summary · context
    Human endothelial cells and keratinocyte cells were used to assess angiogenesis and vascular endothelial growth factor expression in vitro.
  8. 08LabIn vitro (cells)Mechanism

    In human cell assays, Ex-4 increased vascular endothelial growth factor expression.

    In plain wordsIn cells, Ex-4 increased vascular endothelial growth factor expression.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseVEGF expression
    Study

    humann: not reported in source

    Human endothelial and keratinocyte cell assays
    Outcome group
    Receptor activity and mechanism · Skin and wound
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In addition, both Ex-4 and ADSC-CM increased the expression of vascular endothelial growth factor.
    1 context sentence
    Summary · context
    Human endothelial cells and keratinocyte cells were used to assess angiogenesis and vascular endothelial growth factor expression in vitro.

Studies that did not test the peptide alone1

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

  1. 09AnimalNot a test of Exenatide (exendin-4) aloneAnimal study (in vivo)Efficacy outcome

    In mouse wounds, Ex-4 plus ADSCs produced a better therapeutic effect than Ex-4 alone.

    In plain wordsIn mice, Ex-4 plus stem cells improved wound treatment results more than Ex-4 alone.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseCombination therapeutic effect versus Ex-4
    Study

    mousen: not reported in source

    Diabetic and normoglycemic mouse skin wounds
    Comparator
    Ex-4 alone
    Outcome group
    Wound healing · Skin and wound

    Source sentences

    Summary
    A combination of Ex-4 and ADSCs showed a significantly better therapeutic effect over either treatment alone.
    2 context sentences
    Summary · context
    Diabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back.
    Summary · context
    One day after wounding, each wound received ADSCs (2.5 × 105 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

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

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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