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Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis.
Farooqui, Naba; Mohan, Arjunmohan; Isik, Busra; Goksu, Busra B; Thaler, Roman; Zhu, Xiang Yang; Krier, James D; Saadiq, Ishran M; Ferguson, Christopher M; Jordan, Kyra L; Tang, Hui; Textor, Stephen C; Hickson, La Tonya J; van Wijnen, Andre J; Eirin, Alfonso; Lerman, Lilach O; Herrmann, Sandra M.
Afiliación
  • Farooqui N; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Mohan A; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Isik B; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Goksu BB; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Thaler R; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
  • Zhu XY; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Krier JD; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Saadiq IM; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Ferguson CM; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Jordan KL; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Tang H; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Textor SC; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Hickson TJ; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • van Wijnen AJ; Department of Biochemistry, University of Vermont, Burlington, VT, USA.
  • Eirin A; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Lerman LO; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Herrmann SM; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Stem Cells ; 41(1): 50-63, 2023 01 30.
Article en En | MEDLINE | ID: mdl-36250949
Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obstrucción de la Arteria Renal / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Stem Cells Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obstrucción de la Arteria Renal / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Stem Cells Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido