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Cell and Tissue Research

, Volume 368, Issue 3, pp 603–613 | Cite as

Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury

  • Chunwoo Lee
  • Myoung Jin Jang
  • Bo Hyun Kim
  • Jin Young Park
  • Dalsan You
  • In Gab Jeong
  • Jun Hyuk Hong
  • Choung-Soo KimEmail author
Regular Article

Abstract

Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague–Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson’s trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P < 0.001). TUNEL labeling showed significantly decreased apoptosis in both the renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P < 0.001). Thus, renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

Keywords

Ischemia/reperfusion injury Acute kidney injury Stromal vascular fraction Renal function Rat acute kidney injury model 

Abbreviations

AKI

Acute kidney injury

DMEM

Dulbecco’s modified Eagle’s medium

FBS

Fetal bovine serum

GFR

Glomerular filtration rate

GPx

Glutathione peroxidase

GR

Glutathione reductase

I/R

Ischemia/reperfusion

PBS

Phosphate-buffered saline

SVF

Stromal vascular fraction

TUNEL

Terminal-deoxynucleotidyl-transferase-mediated dUTP nick-end labeling

Notes

Compliance with ethical standards

Conflicts of interest

No conflicts are declared.

References

  1. Aird AL, Nevitt CD, Christian K, Williams SK, Hoying JB, LeBlanc AJ (2015) Adipose-derived stromal vascular fraction cells isolated from old animals exhibit reduced capacity to support the formation of microvascular networks. Exp Gerontol 63:18–26CrossRefPubMedPubMedCentralGoogle Scholar
  2. Behr L, Hekmati M, Fromont G, Borenstein N, Noel LH, Lelievre-Pegorier M, Laborde K (2007) Intra renal arterial injection of autologous mesenchymal stem cells in an ovine model in the postischemic kidney. Nephron Physiol 107:p65–p76CrossRefPubMedGoogle Scholar
  3. Bi B, Schmitt R, Israilova M, Nishio H, Cantley LG (2007) Stromal cells protect against acute tubular injury via an endocrine effect. J Am Soc Nephrol 18:2486–2496CrossRefPubMedGoogle Scholar
  4. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15:641–648CrossRefPubMedPubMedCentralGoogle Scholar
  5. Burst VR, Gillis M, Putsch F, Herzog R, Fischer JH, Heid P, Muller-Ehmsen J, Schenk K, Fries JW, Baldamus CA, Benzing T (2010) Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury. Nephron Exp Nephrol 114:e107–e116CrossRefPubMedGoogle Scholar
  6. Casteilla L, Planat-Benard V, Laharrague P, Cousin B (2011) Adipose-derived stromal cells: their identity and uses in clinical trials, an update. World J Stem Cells 3:25–33CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chen YT, Sun CK, Lin YC, Chang LT, Chen YL, Tsai TH, Chung SY, Chua S, Kao YH, Yen CH, Shao PL, Chang KC, Leu S, Yip HK (2011) Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Transl Med 9:51CrossRefPubMedPubMedCentralGoogle Scholar
  8. Dekel B, Shezen E, Even-Tov-Friedman S, Katchman H, Margalit R, Nagler A, Reisner Y (2006) Transplantation of human hematopoietic stem cells into ischemic and growing kidneys suggests a role in vasculogenesis but not tubulogenesis. Stem Cells 24:1185–1193CrossRefPubMedGoogle Scholar
  9. Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T, Bonventre JV (2005) Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 115:1743–1755CrossRefPubMedPubMedCentralGoogle Scholar
  10. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11:367–368CrossRefPubMedGoogle Scholar
  11. Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G (2004) Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 14:1035–1041PubMedGoogle Scholar
  12. Imberti B, Morigi M, Tomasoni S, Rota C, Corna D, Longaretti L, Rottoli D, Valsecchi F, Benigni A, Wang J, Abbate M, Zoja C, Remuzzi G (2007) Insulin-like growth factor-1 sustains stem cell mediated renal repair. J Am Soc Nephrol 18:2921–2928CrossRefPubMedGoogle Scholar
  13. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE (2004a) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 94:678–685CrossRefPubMedGoogle Scholar
  14. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE (2004b) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109:1543–1549CrossRefPubMedGoogle Scholar
  15. La Manna G, Bianchi F, Cappuccilli M, Cenacchi G, Tarantino L, Pasquinelli G, Valente S, Della Bella E, Cantoni S, Claudia C, Neri F, Tsivian M, Nardo B, Ventura C, Stefoni S (2011) Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model. Cell Transplant 20:1193–1208CrossRefPubMedGoogle Scholar
  16. Lange C, Togel F, Ittrich H, Clayton F, Nolte-Ernsting C, Zander AR, Westenfelder C (2005) Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int 68:1613–1617CrossRefPubMedGoogle Scholar
  17. Lanugos O, Wald R, O’Bell JW, Price L, Pereira BJ, Jaber BL (2006) Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol 1:43–51CrossRefGoogle Scholar
  18. Lee PY, Chien Y, Chiou GY, Lin CH, Chiou CH, Tarng DC (2012) Induced pluripotent stem cells without c-Myc attenuate acute kidney injury via downregulating the signaling of oxidative stress and inflammation in ischemia-reperfusion rats. Cell Transplant 21:2569–2585CrossRefPubMedGoogle Scholar
  19. Li B, Cohen A, Hudson TE, Motlagh D, Amrani DL, Duffield JS (2010) Mobilized human hematopoietic stem/progenitor cells promote kidney repair after ischemia/reperfusion injury. Circulation 121:2211–2220CrossRefPubMedPubMedCentralGoogle Scholar
  20. Melnikov VY, Faubel S, Siegmund B, Lucia MS, Ljubanovic D, Edelstein CL (2002) Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest 110:1083–1091CrossRefPubMedPubMedCentralGoogle Scholar
  21. Morigi M, Imberti B, Zoja C, Corna D, Tomasoni S, Abbate M, Rottoli D, Angioletti S, Benigni A, Perico N, Alison M, Remuzzi G (2004) Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol 15:1794–1804CrossRefPubMedGoogle Scholar
  22. Ning H, Liu G, Lin G, Garcia M, Li LC, Lue TF, Lin CS (2009) Identification of an aberrant cell line among human adipose tissue-derived stem cell isolates. Differentiation 77:172–180CrossRefPubMedGoogle Scholar
  23. Shih YC, Lee PY, Cheng H, Tsai CH, Ma H, Tarng DC (2013) Adipose-derived stem cells exhibit antioxidative and antiapoptotic properties to rescue ischemic acute kidney injury in rats. Plast Reconstr Surg 132:940e–951eCrossRefPubMedGoogle Scholar
  24. Silva LB da, Palma PV, Cury PM, Bueno V (2007) Evaluation of stem cell administration in a model of kidney ischemia-reperfusion injury. Int Immunopharmacol 7:1609–1616Google Scholar
  25. Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C (2005) Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol 289:F31–F42CrossRefPubMedGoogle Scholar
  26. Togel F, Weiss K, Yang Y, Hu Z, Zhang P, Westenfelder C (2007) Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am J Physiol Renal Physiol 292:F1626–F1635CrossRefPubMedGoogle Scholar
  27. Togel F, Cohen A, Zhang P, Yang Y, Hu Z, Westenfelder C (2009) Autologous and allogeneic marrow stromal cells are safe and effective for the treatment of acute kidney injury. Stem Cells Dev 18:475–485CrossRefPubMedGoogle Scholar
  28. Wang Y, He J, Pei X, Zhao W (2013) Systematic review and meta-analysis of mesenchymal stem/stromal cells therapy for impaired renal function in small animal models. Nephrology (Carlton) 18:201–208CrossRefGoogle Scholar
  29. Yasuda K, Ozaki T, Saka Y, Yamamoto T, Gotoh M, Ito Y, Yuzawa Y, Matsuo S, Maruyama S (2012) Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells. Cytotherapy 14:1089–1100CrossRefPubMedGoogle Scholar
  30. Yip HK, Chang LT, Wu CJ, Sheu JJ, Youssef AA, Pei SN, Lee FY, Sun CK (2008) Autologous bone marrow-derived mononuclear cell therapy prevents the damage of viable myocardium and improves rat heart function following acute anterior myocardial infarction. Circ J 72:1336–1345CrossRefPubMedGoogle Scholar
  31. You D, Jang MJ, Lee J, Jeong IG, Kim HS, Moon KH, Suh N, Kim CS (2013) Periprostatic implantation of human bone marrow-derived mesenchymal stem cells potentiates recovery of erectile function by intracavernosal injection in a rat model of cavernous nerve injury. Urology 81:104–110CrossRefPubMedGoogle Scholar
  32. You D, Jang MJ, Kim BH, Song G, Lee C, Suh N, Jeong IG, Ahn TY, Kim CS (2015) Comparative study of autologous stromal vascular fraction and adipose-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury. Stem Cells Transl Med 4:351–358CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Chunwoo Lee
    • 1
  • Myoung Jin Jang
    • 2
  • Bo Hyun Kim
    • 3
  • Jin Young Park
    • 3
  • Dalsan You
    • 3
  • In Gab Jeong
    • 3
  • Jun Hyuk Hong
    • 3
  • Choung-Soo Kim
    • 3
    Email author
  1. 1.Department of Urology, Gyeongsang National University Changwon HospitalGyeongsang National University School of MedicineChangwonSouth Korea
  2. 2.Asan Institute for Life Sciences, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  3. 3.Department of Urology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea

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