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Therapeutic Use of Adipose-Derived Stromal Cells in a Murine Model of Acute Pancreatitis

  • Alexandra M. Roch
  • Thomas K. Maatman
  • Todd G. Cook
  • Howard H. Wu
  • Stephanie Merfeld-Clauss
  • Dmitry O. Traktuev
  • Keith L. March
  • Nicholas J. ZyromskiEmail author
2019 SSAT Plenary Presentation

Abstract

Background

No specific therapy exists for acute pancreatitis (AP), and current treatment remains entirely supportive. Adipose stem cells (ASCs) have significant immunomodulatory and regenerative activities. We hypothesized that systemic administration of ASCs would mitigate inflammation in AP.

Methods

AP was induced in mice by 6 hourly intraperitoneal injections of cerulein. Twenty-four hours after AP induction, mice were randomized into four systemic treatment groups: sham group (no acute pancreatitis), vehicle, human ASCs, and human ASC–conditioned media. Mice were sacrificed at 48 h, and blood and organs were collected and analyzed. Pancreatic injury was quantified histologically using a published score (edema, inflammation, and necrosis). Pancreatic inflammation was also studied by immunohistochemistry and PCR.

Results

When using IV infusion of Hoechst-labeled ASCs, ASCs were found to localize to inflamed tissues: lungs and pancreas. Mice treated with ASCs had less severe AP, as shown by a significantly decreased histopathology score (edema, inflammation, and necrosis) (p = 0.001). ASCs infusion polarized pancreatic macrophages toward an anti-inflammatory M2 phenotype. ASC-conditioned media reduced pancreatic inflammation similarly to ASCs only, highlighting the importance of ASCs secreted factors in modulating inflammation.

Conclusion

Intravenous delivery of human ASCs markedly reduces pancreatic inflammation in a murine model of AP ASCs which represent an effective therapy for AP.

Keywords

Acute pancreatitis Murine model Treatment Adipose stem cells 

Notes

Funding Information

This work was supported by the 2016–2017 International Hepato-Pancreato-Biliary Association (IHPBA) Kenneth Warren Fellowship.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  • Alexandra M. Roch
    • 1
  • Thomas K. Maatman
    • 1
  • Todd G. Cook
    • 1
  • Howard H. Wu
    • 2
  • Stephanie Merfeld-Clauss
    • 3
  • Dmitry O. Traktuev
    • 3
  • Keith L. March
    • 3
  • Nicholas J. Zyromski
    • 1
    Email author
  1. 1.Department of SurgeryIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of PathologyIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of Medicine, Division of Cardiovascular Medicine, Center for Regenerative medicineUniversity of FloridaGainesvilleUSA

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