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Abstract: PO0633

Effect of Hypoxic Preconditioning on Angiogenesis and Senescence in Human Adipose Tissue-Derived Mesenchymal Stem Cells

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Mohan, Arjunmohan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Farooqui, Naba, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Isik, Busra, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Zhu, Xiang yang, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Jordan, Kyra L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Saadiq, Ishran M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tang, Hui, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Textor, Stephen C., 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

Hypertension(HTN) and chronic kidney disease(CKD) alter the angiogenic and immunomodulatory properties of human adipose-derived Mesenchymal Stem Cells(AMSC). Hypoxic conditions modify growth potential, paracrine functions and gene expression of AMSCs. We tested the hypothesis that AMSCs in CKD patients,preconditioned with hypoxia,will have reduced senescence,enhanced migratory, proliferative and angiogenic functions compared to healthy kidney donors.

Methods

We cultured AMSCs(P3-4) from healthy kidney donors(Controls), patients with HTN and CKD(n=6 each group) under normoxia(20%O2) and hypoxia(1%O2). We tested AMSC migration and proliferation, quantified angiogenic and inflammatory factors (VEGF,HGF,TNF-α,TGF-β) in cell culture supernatant, and analyzed gene expression(VEGF,HGF,P16,P21) using rt-PCR.

Results

The table shows characteristics of enrolled patients. Hypoxia suppresses AMSC migration in controls and HTN patients while enhancing it in CKD patients and increasing proliferation in all groups. Hypoxia increases VEGF secretion in controls and CKD while downregulating HGF gene expression in controls and HTN group. In CKD patients, TGF-β secretion was higher at baseline and under hypoxia, TNF-α was elevated. Senescence(gene expression of P16/P21) was not different among the groups at baseline but hypoxia attenuated it in all groups.

Conclusion

Hypoxic preconditioning of AMSCs increases migration,proliferation,upregulates VEGF secretion and gene expression, and downregulates pro-senescence genes. These results support hypoxic preconditioning to enhance the regenerative potential and overcome challenges in autologous stem cell therapy for nephropathies.

Funding

  • NIDDK Support