Skip to main content

Advertisement

SpringerLink
Log in

Adipose-derived mesenchymal stem cells transplantation facilitate experimental peritoneal fibrosis repair by suppressing epithelial–mesenchymal transition

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

Prevention or reversal of peritoneal damage is critical in peritoneal dialysis. Although autologous cell transplantation has beneficial effects on tissue repair in various organs, few studies have investigated the effects of transplantation of adipose-derived mesenchymal stem cells (ASCs) on peritoneal fibrosis (PF). Thus, we examined the mechanism of facilitated peritoneal reconstruction induced by ASC transplantation on chlorhexidine gluconate (CG)-induced PF in rats.

Methods

To induce PF in rats, continuous-infusion pumps containing 8 % CG were placed in the abdominal cavity for 21 days. The pumps were removed on day 22 and ASCs were immediately injected into the peritoneal cavity. Morphological alterations and mRNA expression levels of fibrosis-related factors were examined on days 29 and 35.

Results

ASC transplantation significantly facilitated peritoneal repair. mRNA expression of tumor necrosis factor-α, interleukin-1β, monocyte chemotactic protein-1, and epithelial–mesenchymal transition (EMT) markers such as Snail and α-smooth muscle actin were suppressed, whereas that of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB) were overexpressed after ASC transplantation. Immunofluorescence indicated that some transplanted ASCs expressed VEGF and PDGF-BB and differentiated into vascular cells.

Conclusions

ASC transplantation facilitates peritoneal repair by suppressing EMT and modulating inflammation and angiogenesis during the early phase of tissue repair in experimental PF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kawaguchi Y, Saito A, Kawanishi H et al (2005) Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures. Perit Dial Int 25(Suppl 4):S83–S95

    PubMed  Google Scholar 

  2. Schilte MN, Celie JW, Wee PM et al (2009) Factors contributing to peritoneal tissue remodeling in peritoneal dialysis. Perit Dial Int 29(6):605–617

    PubMed  CAS  Google Scholar 

  3. Io H, Hamada C, Ro Y et al (2004) Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models. Kidney Int 65(5):1927–1936

    Article  PubMed  CAS  Google Scholar 

  4. Giannoni E, Parri M, Chiarugi P (2012) EMT and oxidative stress: a bidirectional interplay affecting tumor malignancy. Antioxid Redox Signal 16:1248–1263

    Article  PubMed  CAS  Google Scholar 

  5. Prockop DJ (2009) Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 17(6):939–946

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Prockop DJ, Kota DJ, Bazhanov N et al (2010) Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med 14(9):2190–2199

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  PubMed  CAS  Google Scholar 

  8. Prockop DJ, Oh JY (2012) Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther 20(1):14–20

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Parfenova H, Leffler CW, Tcheranova D et al (2010) Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage. Am J Physiol Heart Circ Physiol 298(6):H1687–H1698

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Nagaya N, Kangawa K, Itoh T et al (2005) Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112(8):1128–1135

    Article  PubMed  Google Scholar 

  11. Ortiz LA, Gambelli F, McBride C et al (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 100(14):8407–8411

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Ninichuk V, Gross O, Segerer S et al (2006) Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int 70(1):121–129

    Article  PubMed  CAS  Google Scholar 

  13. Sekiguchi Y, Hamada C, Ro Y et al (2012) Differentiation of bone marrow-derived cells into regenerated mesothelial cells in peritoneal remodeling using a peritoneal fibrosis mouse model. J Artif Organs 15(3):272–282

    Article  PubMed  CAS  Google Scholar 

  14. Ueno T, Nakashima A, Doi S et al (2013) Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-beta1 signaling. Kidney Int 84(2):297–307

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Wang N, Li Q, Zhang L et al (2012) Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6. PLoS ONE 7(8):e43768

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Bastug F, Gunduz Z, Tulpar S et al (2013) Mesenchymal stem cell transplantation may provide a new therapy for ultrafiltration failure in chronic peritoneal dialysis. Nephrol Dial Transplant 28(10):2493–2501

    Article  PubMed  CAS  Google Scholar 

  17. Banas A, Teratani T, Yamamoto Y et al (2008) IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 26(10):2705–2712

    Article  PubMed  CAS  Google Scholar 

  18. Leu S, Lin YC, Yuen CM et al (2010) Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats. J Transl Med 8:63

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chen YT, Sun CK, Lin YC et al (2011) Adipose-derived mesenchymal stem cell protects kidneys against ischemia–reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Transl Med 9:51

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Takahashi M, Suzuki E, Oba S et al (2010) Adipose tissue-derived stem cells inhibit neointimal formation in a paracrine fashion in rat femoral artery. Am J Physiol Heart Circ Physiol 298(2):H415–H423

    Article  PubMed  CAS  Google Scholar 

  21. Kanda R, Hamada C, Kaneko K et al (2014) Paracrine effects of transplanted mesothelial cells isolated from temperature-sensitive SV40 large T antigen gene transgenic rats during peritoneal repair. Nephrol Dial Transplant 29(2):289–300

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Komatsu H, Uchiyama K, Tsuchida M et al (2008) Development of a peritoneal sclerosis rat model using a continuous-infusion pump. Perit Dial Int 28(6):641–647

    PubMed  Google Scholar 

  23. Lopez MJ, Spencer ND (2011) In vitro adult rat adipose tissue-derived stromal cell isolation and differentiation. Methods Mol Biol 702:37–46

    Article  PubMed  CAS  Google Scholar 

  24. Honda K, Hamada C, Nakayama M et al (2008) Impact of uremia, diabetes, and peritoneal dialysis itself on the pathogenesis of peritoneal sclerosis: a quantitative study of peritoneal membrane morphology. Clin J Am Soc Nephrol 3(3):720–728

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shimaoka T, Hamada C, Kaneko K et al (2010) Quantitative evaluation and assessment of peritoneal morphologic changes in peritoneal dialysis patients. Nephrol Dial Transplant 25(10):3379–3385

    Article  PubMed  Google Scholar 

  26. Selgas R, Bajo A, Jimenez-Heffernan JA et al (2006) Epithelial-to-mesenchymal transition of the mesothelial cell—its role in the response of the peritoneum to dialysis. Nephrol Dial Transplant. 21 Suppl 2:ii2–ii7

    PubMed  Google Scholar 

  27. Kapitsinou PP, Jaffe J, Michael M et al (2012) Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury. Am J Physiol Renal Physiol 302(9):F1172–F1179

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22(10):1276–1312

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Pierce GF, Tarpley JE, Allman RM et al (1994) Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB. Am J Pathol 145(6):1399–1410

    PubMed  CAS  PubMed Central  Google Scholar 

  30. Szoke K, Brinchmann JE (2012) Concise review: therapeutic potential of adipose tissue-derived angiogenic cells. Stem Cells Transl Med 1(9):658–667

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Gehmert S, Gehmert S, Hidayat M et al (2011) Angiogenesis: the role of PDGF-BB on adipose-tissue derived stem cells (ASCs). Clin Hemorheol Microcirc 48(1):5–13

Download references

Acknowledgments

This study was supported by Grants-in-Aid for science from the Ministry of Education, Culture, Sport, Science, and Technology of Japan. We thank Terumi Shibata for her excellent technical assistance. We also thank Takako Ikegami and Tomomi Ikeda (Division of Molecular and Biochemical Research, Juntendo University Graduate School of Medicine) for their excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Keiichi Wakabayashi, Chieko Hamada, Reo Kanda, Takanori Nakano, Hiroaki Io, Satoshi Horikoshi & Yasuhiko Tomino

Authors
  1. Keiichi Wakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chieko Hamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reo Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takanori Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroaki Io
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoshi Horikoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuhiko Tomino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiko Tomino.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wakabayashi, K., Hamada, C., Kanda, R. et al. Adipose-derived mesenchymal stem cells transplantation facilitate experimental peritoneal fibrosis repair by suppressing epithelial–mesenchymal transition. J Nephrol 27, 507–514 (2014). https://doi.org/10.1007/s40620-014-0133-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-014-0133-5

Keywords

Search

Navigation