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Abstract: FR-PO398

Hypoxia Preconditioning improves Angiogenic and Inflammatory Gene Profile of Adipose Derived Mesenchymal Stem Cells in Hypertensive Kidney Disease

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
  • Ahsan, Eram, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sandoval, Leticia Assad Maia, 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

Hypertensive kidney disease(HKD) in the setting of uremic milieu may alter the reparative potential of autologous adipose derived mesenchymal stem cells(AMSC) but might be improved by hypoxic preconditioning(HPC). We hypothesize that the state of HKD and not hypertension per se worsens the gene expression profile of AMSC compared to AMSC from patients with essential hypertension without CKD(HTN) as well as healthy controls(HC) and we examined if HPC attenuates that.

Methods

We cultured human AMSC(P3-4) isolated from healthy kidney donors(HC), HTN and HKD(n=3 each) under normoxia(20% O2) and hypoxia(1% O2). mRNA sequencing was performed on AMSC cell pellets and counts were normalized using edgeR software(v3.28.1). Genes with significant log fold change(p<0.05 and >1.4 for up- or down-regulation) were grouped based on gene sets available on Mouse Genome Informatics database.

Results

The baseline characteristics of the patients are shown in Table 1. On comparing HKD vs HC, inflammatory genes TLR3, CXCL1, CXCL2, and CXCL3 were significantly upregulated and a greater % of angiogenic genes are downregulated than upregulated(Fig. 1A). HPC promoted upregulation of angiogenic genes including vascular endothelial growth factor A (VEGF A), anti-inflammatory genes like Interleukin-1 receptor antagonist protein and nuclear factor kappa-B (NF-kB) inhibitors(Fig. 1C). Similarly, in HTN the inflammatory genes CXCL1, CXCL2, CXCL5, CXCL12, and TNF alpha-induced proteins were upregulated versus HC(Fig. 1B), and HPC abolished their upregulation. HKD showed a greater percentage downregulation of angiogenic genes compared to HTN which was reversed by HPC(Fig. 1D).

Conclusion

HKD and HTN are associated with upregulation of RNA levels of inflammatory genes in AMSC as compared ot HC, with HKD showing decreased angiogenic gene profile compared to HTN. HPC may serve as a strategy to attenuate this response and enhance the angiogenic and anti-inflammatory gene expression profile of these AMSC.

Funding

  • NIDDK Support