Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis

• DOI: 10.1093/stmcls/sxac073
• Publication Date: 2022-10-17T18:42:52Z
• Authors: Naba Farooqui; Arjunmohan Mohan; Busra Isik; Busra B Goksu; Roman Thaler; Xiang Yang Zhu; James D Krier; Ishran M Saadiq; Christopher M Fer...; Kyra L Jordan; Hui Tang; Stephen C Textor; La Tonya J Hickson; Andre J van Wijnen; Alfonso Eirin; Lilach O Lerman; Sandra M Herrmann
• Keywords: Hypoxia

Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal disease and regenerative stem cell therapies may improve outcomes. Hypoxia preconditioning (HPC) the functions of adipose tissue-derived mesenchymal cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth AMSCs hypoxia (Hx) versus normoxia (Nx) would enhance tissue repair, comprehensively analyze how HPC modifies hydroxymethylation compared to untreated healthy/normal pigs (n=5 each). exhibited elevated serum cholesterol, creatinine stenosis, concomitant decrease blood flow (RBF) increased pressure (BP) healthy pigs. Renal injection either autologous Nx or Hx improved diastolic BP, reduced kidney fibrosis, inflammation (CD3+ T-cells) In addition, medullary significantly lowered but not AMSC treatment. Mechanistically, levels epigenetic 5hmC (which reflect gene activation) estimated immunoprecipitation technique were profibrotic inflammatory genes normal AMSCs. cholesterol biosynthesis oxidative stress response pathways Thus, key renovascular parameters pigs, mitigating pathological molecular effects on which play role augmenting capacity