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J Gastrointest Surg. 2020 Jan;24(1):67-75. doi: 10.1007/s11605-019-04411-w. Epub 2019 Nov 19.

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

Author information

1
Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive EH 519, Indianapolis, IN, 46202, USA.
2
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
3
Department of Medicine, Division of Cardiovascular Medicine, Center for Regenerative medicine, University of Florida, Gainesville, FL, USA.
4
Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive EH 519, Indianapolis, IN, 46202, USA. nzyromsk@iupui.edu.

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; Adipose stem cells; Murine model; Treatment

PMID:
31745900
DOI:
10.1007/s11605-019-04411-w

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