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. Zyromski

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of Gastrointestinal Surgery
DOIs
StateAccepted/In press - Jan 1 2019

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Therapeutic Uses
Stromal Cells
Pancreatitis
Stem Cells
Inflammation
Edema
Necrosis
Ceruletide
Stem Cell Factor
Conditioned Culture Medium
Intraperitoneal Injections
Pancreas
Anti-Inflammatory Agents
Therapeutics
Immunohistochemistry
Macrophages
Placebos
Phenotype
Polymerase Chain Reaction
Lung

Keywords

  • Acute pancreatitis
  • Adipose stem cells
  • Murine model
  • Treatment

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

Therapeutic Use of Adipose-Derived Stromal Cells in a Murine Model of Acute Pancreatitis. / Roch, Alexandra M.; Maatman, Thomas K.; Cook, Todd G.; Wu, Howard H.; Merfeld-Clauss, Stephanie; Traktuev, Dmitry O.; March, Keith L.; Zyromski, Nicholas J.

In: Journal of Gastrointestinal Surgery, 01.01.2019.

Research output: Contribution to journalArticle

Roch, Alexandra M. ; Maatman, Thomas K. ; Cook, Todd G. ; Wu, Howard H. ; Merfeld-Clauss, Stephanie ; Traktuev, Dmitry O. ; March, Keith L. ; Zyromski, Nicholas J. / Therapeutic Use of Adipose-Derived Stromal Cells in a Murine Model of Acute Pancreatitis. In: Journal of Gastrointestinal Surgery. 2019.
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