Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases |
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Institution: | 1. Unité INSERM U965 (Université Paris 7), équipe “Angiogénèse et Recherche Translationnelle,” Hôpital Lariboisière, Paris, France;2. Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France;3. Paris Cardiovascular Research Center (PARCC), INSERM U970, Hôpital Européen Georges Pompidou, Paris, France;4. Service d’Anatomo-pathologie, Hôpital Lariboisière, Paris, France;5. IFR 65, PlateForme Cytométrie, Hôpital Saint-Antoine, Paris, France;6. Service de Chirurgie Digestive et Cancérologique, Assistance Publique des Hôpitaux de Paris, Hôpital Lariboisière, Paris, France;1. Department of Surgery, The University of Hong Kong, Hong Kong, China;2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China;3. Shenzhen Institute of Research and Innovation, The University of Hong Kong, China;4. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong city, 226001, China;5. Department of Medicine, The University of Hong Kong, Hong Kong, China;6. Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China;7. Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, USA;1. Chairman of Liver Transplant Program, Sanatorio Trinidad Mitre & Vice-Chairman Liver Transplant Program, Hospital Dr Cosme Argerich, Buenos Aires, Argentina;2. Chairman of Liver Transplant Program, Hospital Juan P Garrahan & Chairman of Liver Transplant Program, Hospital Dr Cosme Argerich, Buenos Aires, Argentina;3. Head of Liver Transplant Surgery and Acting Head Transplant Services, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia;4. Digestive Organs Transplant Division, Gastroenterology Department, São Paulo University School of Medicine, São Paulo, Brazil;5. Digestive Organs Transplant Division, Gastroenterology Department, São Paulo University School of Medicine, São Paulo, Brazil;6. Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, New York, USA;7. Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, New York, USA;8. Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, New York, USA;9. Hepatic-biliary-pancreatic Surgery Department, First Affiliated Hospital of Zhejiang University School of Medicine, China;10. Department of Surgery, Universidad de la Sabana Clinica de la Costa Chief, Transplant Surgery Department, Barranquilla, Colombia;11. Department of Hepatology and Gastroenterology, Medical Director Liver Transplantation Program, Prague, Czech Republic;12. Head of Department of Transplantation Surgery, Surgical Director Liver Transplantation Program, Prague, Czech Republic;13. Medical Staff, Eurotransplant International, Leiden, the Netherlands;14. Manager Allocation, Eurotransplant International, Leiden, the Netherlands;15. Department of Digestive Surgery & Liver Transplantation, Croix Rousse University Hospital, Hospices Civils de Lyon, University Lyon 1, Lyon, France;16. Department of Digestive Surgery & Liver Transplantation, Croix Rousse University Hospital, Hospices Civils de Lyon, University Lyon 1, Lyon, France;17. Department of Surgical Gastroenterology, Jaslok Hospital & Research Centre, Mumbai, India;18. Visceral Transplant Surgeon, Associate Professor of Surgery, Tabriz University of Medical Sciences, Tabriz, Iran;19. President of Iranian Society for Organ Transplantation, Shiraz University of Medical Sciences, Shiraz, Iran;20. Department of Surgery, Tokyo Women''s Medical University, Tokyo, Japan;21. Transplant Surgeon, Associate Professor in Transplantation, National Institute of Medical Sciences and Nutrition Salvador Zubirán, National and Autonomous University of Mexico, Mexico;22. Polish Transplant Coordinating Center Poltransplant, Warsaw, Poland;23. Polish Transplant Coordinating Center Poltransplant, Warsaw, Poland;24. Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, CHLC, Lisbon, Portugal;25. Director of National Medical Research Center of Transplantology and Artificial Organs named after academician V.I. Shumakov, Sechenov University, Moscow, Russian Federation;26. Department of Surgery, National Medical Research Center of Transplantology and Artificial Organs named after academician V.I. Shumakov, Sechenov University, Moscow, Russian Federation;27. Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway;28. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway;29. Institute of Clinical Medicine, University of Oslo, Oslo, Norway;30. Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway;31. Chairman Scandiatransplant, Department of Transplantation Surgery, Karolinska University Hospital, Huddinge, Sweden;32. Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Keimyung University Dong-San Medical Center, Daegu, Republic of Korea;33. Professor MD PhD, Department of Surgery, College of Medicine, Yonsei University, Seoul, Republic of Korea;34. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;35. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;36. Department of Gastroenterology, University Hospital of Zurich, Zurich, Switzerland;37. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;38. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;39. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;40. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;41. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;42. Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;43. Division of Transplantation, Baskent University, Ankara, Turkey;44. Liver Transplant Institute, Inonu University, Malatya, Turkey;45. St James’s University Hospital, University of Leeds, Leeds, England, United Kingdom;46. HPB and Transplant Unit, St James’s University Hospital, Leeds LS9 7TF, England, United Kingdom;1. Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland;2. Multivisceral Transplant Unit - Gastroenterology, Padua University Hospital, Padua, Italy;1. Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH;2. Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH;3. Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL;4. Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH |
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Abstract: | BackgroundHepatic pedicle clamping is often required to reduce blood loss and transfusion during liver resection. However, the question remains whether use of hepatic pedicle clamping promotes tumor growth. Endothelial progenitor cells (EPCs) are mobilized from bone marrow in response to tissue ischemia, which allows neovascularization of ischemic tissue. It has been suggested that EPCs are involved in tumor progression. We hypothesized that hepatic ischemia reperfusion (I/R)-induced mobilization of EPCs could enhance growth of microscopic tumor, therefore promoting liver metastasis in a mouse model of colorectal cancer.Materials and methodsWe used mouse models of hepatic I/R and hind limb ischemia. For comparison, we studied mice that underwent limb ischemia as positive controls of EPC mobilization. At day 0, we divided 40 mice into four groups: hepatic I/R, hind limb ischemia, combined hepatic I/R and hind limb ischemia, and control (sham midline incision laparotomy). At day 2, we induced liver metastasis in all mice by injecting CT-26 cells into the spleen. Time-dependent circulating EPCs were determined by flow cytometry. We evaluated liver metastasis and microvascular density on day 21.ResultsThe number of circulating progenitor cells increased rapidly in the ischemic groups compared with the control group. Hepatic I/R significantly increased tumor outgrowth compared with the control group. Increased tumor growth was associated with enhanced CD31-positive microvascular density in liver tissue.ConclusionsHepatic I/R leads to mobilization of bone marrow–derived EPCs and enhanced intra-hepatic angiogenesis, which is associated with increased tumor burden in an animal model of colorectal liver metastasis. |
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