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

  • 2019 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

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.

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Funding

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

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Authors and Affiliations

  1. Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive EH 519, Indianapolis, IN, 46202, USA

    Alexandra M. Roch, Thomas K. Maatman, Todd G. Cook & Nicholas J. Zyromski

  2. Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA

    Howard H. Wu

  3. Department of Medicine, Division of Cardiovascular Medicine, Center for Regenerative medicine, University of Florida, Gainesville, FL, USA

    Stephanie Merfeld-Clauss, Dmitry O. Traktuev & Keith L. March

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  1. Alexandra M. Roch
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  2. Thomas K. Maatman
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Roch, A.M., Maatman, T.K., Cook, T.G. et al. Therapeutic Use of Adipose-Derived Stromal Cells in a Murine Model of Acute Pancreatitis. J Gastrointest Surg 24, 67–75 (2020). https://doi.org/10.1007/s11605-019-04411-w

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