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Clinical and Experimental Nephrology

, Volume 16, Issue 5, pp 679–689 | Cite as

Effects of adipose-derived mesenchymal cells on ischemia–reperfusion injury in kidney

  • Kengo Furuichi
  • Hidemi Shintani
  • Yoshio Sakai
  • Takahiro Ochiya
  • Kouji Matsushima
  • Shuichi Kaneko
  • Takashi Wada
Original Article

Abstract

Background

Acute kidney injury (AKI) is a critical condition for kidney and other remote organs, including the lung. However, available treatments for AKI are limited. In this study, we explored the effect of adipose-derived mesenchymal cells on a mouse model of AKI.

Methods

Adipose-derived mesenchymal cells were isolated from mouse subcutaneous and peritoneal adipose tissue by digestion with collagenase type I. The left renal artery and vein of C57BL/6 mice were clamped for 45 min to induce ischemia and were injected with the adipose-derived mesenchymal cells [1 × 105 cells/0.2 ml phosphate-buffered saline (PBS)] or 0.2 ml PBS via the tail vein on days 0, 1, and 2.

Results

The adipose-derived mesenchymal cells had stem-cell surface markers and multilineage differentiating potentials. Administered adipose-derived mesenchymal cells homed primarily into lung. Interestingly, repeated administration of adipose-derived mesenchymal cells reduced acute tubular necrosis and interstitial macrophage infiltration in the injured kidney, accompanied with reduced cytokine and chemokine expression.

Conclusion

Adipose-derived mesenchymal cells can be used as cell-based therapy for ischemic kidney injury.

Keywords

Acute kidney injury Ischemic kidney injury Adipose-derived mesenchymal cells Chemokines 

Notes

Acknowledgments

The work was financially supported in part by grants-in-aids from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government.

Conflict of interest

None.

Reference

  1. 1.
    Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100:1249–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48:1416–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Ochiya T, Yamamoto Y, Banas A. Commitment of stem cells into functional hepatocytes. Differentiation. 2010;79:65–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee SW, Padmanabhan P, Ray P, Gambhir SS, Doyle T, Contag C, Goodman SB, Biswal S. Stem cell-mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury. J Orthop Res. 2009;27:295–302.PubMedCrossRefGoogle Scholar
  5. 5.
    Ishikawa T, Banas A, Hagiwara K, Iwaguro H, Ochiya T. Stem cells for hepatic regeneration: the role of adipose tissue derived mesenchymal stem cells. Curr Stem Cell Res Ther. 2010;5:182–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kato T, Okochi H, Ochiya T. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J Gastroenterol Hepatol. 2009;24:70–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Furuichi K, Wada T, Yokoyama H, Kobayashi KI. Role of cytokines and chemokines in renal ischemia-reperfusion injury. Drug News Perspect. 2002;15:477–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Furuichi K, Wada T, Kaneko S, Murphy PM. Roles of chemokines in renal ischemia/reperfusion injury. Front Biosci. 2008;13:4021–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Furuichi K, Kaneko S, Wada T. Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidney disease. Clin Exp Nephrol. 2009;13:9–14.PubMedCrossRefGoogle Scholar
  10. 10.
    Wada T, Sakai N, Sakai Y, Matsushima K, Kaneko S, Furuichi K. Involvement of bone-marrow-derived cells in kidney fibrosis. Clin Exp Nephrol. 2011;15:8–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Furuichi K, Gao JL, Murphy PM. Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury. Am J Pathol. 2006;169:372–87.PubMedCrossRefGoogle Scholar
  12. 12.
    Paladino JD, Hotchkiss JR, Rabb H. Acute kidney injury and lung dysfunction: a paradigm for remote organ effects of kidney disease? Microvasc Res. 2009;77:8–12.PubMedCrossRefGoogle Scholar
  13. 13.
    Doi K, Ishizu T, Fujita T, Noiri E. Lung injury following acute kidney injury: kidney-lung crosstalk. Clin Exp Nephrol. 2011;15:464–70.Google Scholar
  14. 14.
    Hasper D, von Haehling S, Storm C, Jorres A, Schefold JC. Changes in serum creatinine in the first 24 hours after cardiac arrest indicate prognosis: an observational cohort study. Crit Care. 2009;13:R168.PubMedCrossRefGoogle Scholar
  15. 15.
    Ishani A, Xue JL, Himmelfarb J, Eggers PW, Kimmel PL, Molitoris BA, Collins AJ. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol. 2009;20:223–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H, Ochiya T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 2007;46:219–28.PubMedCrossRefGoogle Scholar
  17. 17.
    Schaffler A, Buchler C. Concise review: adipose tissue-derived stromal cells—basic and clinical implications for novel cell-based therapies. Stem Cells. 2007;25:818–27.PubMedCrossRefGoogle Scholar
  18. 18.
    Lecka-Czernik B, Gubrij I, Moerman EJ, Kajkenova O, Lipschitz DA, Manolagas SC, Jilka RL. Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2. J Cell Biochem. 1999;74:357–71.PubMedCrossRefGoogle Scholar
  19. 19.
    Malaval L, Modrowski D, Gupta AK, Aubin JE. Cellular expression of bone-related proteins during in vitro osteogenesis in rat bone marrow stromal cell cultures. J Cell Physiol. 1994;158:555–72.PubMedCrossRefGoogle Scholar
  20. 20.
    Maniatopoulos C, Sodek J, Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res. 1988;254:317–30.PubMedCrossRefGoogle Scholar
  21. 21.
    Sugiki T, Uyama T, Toyoda M, Morioka H, Kume S, Miyado K, Matsumoto K, Saito H, Tsumaki N, Takahashi Y, Toyama Y, Umezawa A. Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts. J Cell Biochem. 2007;100:1240–54.PubMedCrossRefGoogle Scholar
  22. 22.
    Furuichi K, Gao JL, Horuk R, Wada T, Kaneko S, Murphy PM. Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia–reperfusion injury. J Immunol. 2008;181:8670–6.PubMedGoogle Scholar
  23. 23.
    Lee RH, Seo MJ, Pulin AA, Gregory CA, Ylostalo J, Prockop DJ. The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood. 2009;113:816–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5:54–63.PubMedCrossRefGoogle Scholar
  25. 25.
    Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, Strieter RM, Rosin DL, Okusa MD. IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest. 2010;120:331–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Furuichi K, Wada T, Kitajikma S, Toyama T, Okumura T, Hara A, Kawachi H, Shimizu F, Sugaya T, Mukaida N, Narumi S, Matsushima K, Kaneko S. IFN-inducible protein 10 (CXCL10) regulates tubular cell proliferation in renal ischemia–reperfusion injury. Nephron Exp Nephrol. 2008;109:c29–38.PubMedCrossRefGoogle Scholar
  27. 27.
    Furuichi K, Wada T, Iwata Y, Kokubo S, Hara A, Yamahana J, Sugaya T, Iwakura Y, Matsushima K, Asano M, Yokoyama H, Kaneko S. Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia–reperfusion injury. Crit Care Med. 2006;34:2447–55.PubMedCrossRefGoogle Scholar
  28. 28.
    Furuichi K, Wada T, Iwata Y, Sakai N, Yoshimoto K, Kobayashi Ki K, Mukaida N, Matsushima K, Yokoyama H. Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice. Nephrol Dial Transpl. 2002;17:399–407.CrossRefGoogle Scholar
  29. 29.
    Furuichi K, Wada T, Iwata Y, Kitagawa K, Kobayashi K, Hashimoto H, Ishiwata Y, Tomosugi N, Mukaida N, Matsushima K, Egashira K, Yokoyama H. Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia–reperfusion injury. J Am Soc Nephrol. 2003;14:1066–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Klein CL, Hoke TS, Fang WF, Altmann CJ, Douglas IS, Faubel S. Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int. 2008;74:901–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Liu M, Liang Y, Chigurupati S, Lathia JD, Pletnikov M, Sun Z, Crow M, Ross CA, Mattson MP, Rabb H. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol. 2008;19:1360–70.PubMedCrossRefGoogle Scholar
  32. 32.
    Lin CY, Kao KC, Tian YC, Jenq CC, Chang MY, Chen YC, Fang JT, Huang CC, Tsai YH, Yang CW. The RIFLE score increases the accuracy of outcome prediction in patients with acute respiratory distress syndrome undergoing open lung biopsy. Respiration. 2009;77:398–406.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  • Kengo Furuichi
    • 1
  • Hidemi Shintani
    • 2
  • Yoshio Sakai
    • 3
  • Takahiro Ochiya
    • 4
  • Kouji Matsushima
    • 5
  • Shuichi Kaneko
    • 2
  • Takashi Wada
    • 3
  1. 1.Division of Blood PurificationKanazawa University HospitalKanazawaJapan
  2. 2.Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  3. 3.Department of Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  4. 4.Section for Studies on MetastasisNational Cancer Center Research InstituteTokyoJapan
  5. 5.Department of Molecular Preventive Medicine, Graduate School of MedicineThe University of TokyoTokyoJapan

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