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Age-associated differences in macrophage response in a vaginal wound healing rat model

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A Commentary to this article was published on 11 March 2020

Abstract

Introduction and hypothesis

Surgical treatment of pelvic organ prolapse often includes the use of patients’ vaginal connective tissue. Wound healing appears to play an important part in the success of such procedures. The aim of this study was to describe the effect of age on inflammatory processes, specifically macrophage response, involved in vaginal wound healing.

Methods

Twenty-five young (12 weeks old) and 25 old (12 months old) virgin female Fischer rats underwent a standardized 9-mm posterior midline vaginal incision. Tissue samples were taken for histological analysis on days 1, 3, 7, 14 and 30 post-injury. Parameters evaluated included wound area, macrophage number and expression of inflammatory markers including tumor necrosis factor alpha (TNFa), inducible nitric oxide synthase (iNOS), CCR7/CD197, arginase I and CD163/M130.

Results

Microscopic examination of the vaginal wounds over time demonstrated a clear difference between young and old rats in spontaneous healing capacity. The average wound area in young rats 1 day after injury was significantly smaller than in old rats (16.5 ± 1.7 vs. 23.8 ± 1.5 mm2, P < 0.05). At 3 days post-injury, wounds were closed in young rats but still open in old rats (wound area: 13.5 ± 1.5 mm2). Old rats demonstrated a more excessive and sustained macrophage response compared with young rats. They also demonstrated a disordered pattern of macrophage expression over time, with a prolonged expression of TNFa and iNOS in the tissue and a disordered M2 macrophage response.

Conclusion

Excessive and prolonged macrophage response in older rats may contribute to poor wound healing in the vagina.

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Authors and Affiliations

  1. The Hadassah Human Embryonic Stem Cell Research Center, Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Hospital, Jerusalem, Israel

    Ofra Ben Menachem-Zidon & Benjamin Reubinoff

  2. Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel

    Ilana Parkes, Henry H. Chill, Benjamin Reubinoff & David Shveiky

  3. Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, PO Box 12000, Ein Kerem, Jerusalem, Israel

    Henry H. Chill & David Shveiky

  4. Center for the Study of Sex Differences in Health, Aging and Disease (CSD), Georgetown University, Washington, DC, USA

    Kathryn Sandberg & Hong Ji

Authors
  1. Ofra Ben Menachem-Zidon
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  2. Ilana Parkes
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  3. Henry H. Chill
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  4. Benjamin Reubinoff
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  5. Kathryn Sandberg
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  6. Hong Ji
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  7. David Shveiky
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Contributions

Ben Menachem-Zidon: Project development, data collection, data analysis, manuscript writing and editing.

Parkes: Project development, data analysis, manuscript writing and editing.

Chill: Data analysis, manuscript writing and editing.

Reubinoff: Project management, manuscript editing.

Sandberg: Project development, manuscript editing.

Ji: Data collection, project management.

Shveiky: Project development, data management, data analysis, manuscript writing and editing.

Corresponding author

Correspondence to Henry H. Chill.

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Ben Menachem-Zidon, O., Parkes, I., Chill, H.H. et al. Age-associated differences in macrophage response in a vaginal wound healing rat model. Int Urogynecol J 31, 1803–1809 (2020). https://doi.org/10.1007/s00192-020-04266-9

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  • DOI: https://doi.org/10.1007/s00192-020-04266-9

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