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Abstract: PO0634

Effect of Hypoxia on the Regenerative Capacity of Adipose Tissue-Derived Mesenchymal Stem Cells in an Experimental Model of Atherosclerotic Renal Artery Stenosis

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Farooqui, Naba, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Mohan, Arjunmohan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Zhu, Xiang yang, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Saadiq, Ishran M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ferguson, Christopher M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Jordan, Kyra L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tang, Hui, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Textor, Stephen C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Atherosclerotic renal artery stenosis(ARAS) is a risk factor for parenchymal renal disease.Autologous mesenchymal stem cells(MSC) therapy reduces kidney fibrosis and inflammation in ARAS.Studies have shown that hypoxia preconditioning(Hx) improves MSC function by affecting DNA hydroxymethylation(5-hmC). But the effect of Hx MSCs in vivo ARAS model has not been evaluated.We hypothesize that Hx MSCs would improve renal histology better than normoxic(Nx) MSCs and also compare 5-hmC differences between MSC groups.

Methods

MSCs isolated from abdominal fat of ARAS pigs were cultured under normoxia(20%O2) or hypoxia(1%O2) till 70-80% confluence.Autologous Nx or Hx MSCs(107 cells each) were injected into the swine renal artery 6 wks after induction of ARAS(N=4 each) and compared to Normal and Untreated ARAS pigs(N=5 each).4 wks later, ex-vivo renal trichrome and CD3(T-cell)staining was performed.MSC gene groups with significant 5-hmC fold change levels were grouped on Panther's database.

Results

ARAS pigs treated with either Nx or Hx MSC show reduced renal fibrosis and interstitial inflammation(CD3 cells) versus untreated ARAS pigs(Fig1A,1B).Interstitial fibrosis was less with Nx MSC therapy versus Hx MSC therapy(Fig1A).Interstitial inflammation shows a decreasing trend with Hx MSC therapy versus Nx MSC therapy(p=0.09).Epigenetic analysis showed higher DNA 5-hmC levels of profibrotic and inflammatory genes in ARAS MSC versus Normal Pig MSC(Fig1C).5-hmC levels of some of these genes were lower in Hx MSC(Fig1D).

Conclusion

In swine model of ARAS,intra-arterial renal delivery of autologous MSCs with or without hypoxia preconditioning reduces kidney fibrosis and interstitial Tcell infiltration.Hx MSCs’ effect was not different from Nx MSC.But, enhanced DNA hydroxymethylation of profibrotic and inflammatory genes in ARAS MSC could be mitigated by hypoxia preconditioning.

Funding

  • NIDDK Support