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Abstract: TH-OR135

Dose Related Effects of Intra-Renal Autologous Mesenchymal Stem/Stromal Cell Infusion on Renal Hemodynamics, Function, and Cytokine Signaling in Human Atherosclerotic Renovascular Disease

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 502 Development, Stem Cells, and Regenerative Medicine: Clinical

Authors

  • Abumoawad, Abdelrhman, Mayo Clinic, Rochester, Minnesota, United States
  • Saad, Ahmed, Mayo Clinic, Rochester, Minnesota, United States
  • Ferguson, Christopher M., Mayo Clinic, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo Clinic, Rochester, Minnesota, United States
  • Misra, Sanjay, Mayo Clinic , Rochester, Minnesota, United States
  • Dietz, Allan B., Mayo Clinic , Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States
  • Textor, Stephen C., Mayo Clinic, Rochester, Minnesota, United States
Background

Preliminary data identify increased renal blood flow after intra-renal infusion of mesenchymal stem/stromal cells (MSC) in post-stenotic kidneys. The effects of cell dose on systemic effects and anti-inflammatory activity of autologous MSC in human renovascular disease (RVD) are poorly understood

Methods

We measured cortical and medullary blood flows (MDCT), GFR (iothalamate and eGFR), renal vein cytokine levels, BP, and tissue oxygenation (BOLD MR) in 21 human subjects with atherosclerotic RVD under controlled study conditions, before and 3 mo after MSC delivery. Autologous adipose-derived MSC were administered at 3 dose levels (1, 2.5 and 5.0x105/MSC/kg, n=7 patients each) into one affected kidney, without vascular intervention. Cultured MSC were also studied in vitro..

Results

At the highest dose (5x105 cells/kg), systolic BP fell (140±11.8 to 128±8.18 mmHg, p<.01), as did urine protein (149±89 to 103±96 mg/dL, p<.01), while single kidney GFR rose (18±10.6 to 21±12.5 ml/min, p<.05). Serum creatinine and renal venous VEGF-A fell only in the highest dose (Figure), whereas VEGF-C and Angiopontin fell at all dose ranges.
Increases in treated-kidney tissue oxygenation by BOLD MR were correlated with levels of hepatocyte growth factor secretion by MSC in vitro.

Conclusion

These data reinforce the capability of autologous MSC to improve the renal circulation in human RVD, and reveal their potential to improve renal function, decrease BP, and modify angiogenic signaling from post-stenotic kidneys. The observation that some beneficial effects are dose-dependent and related to in-vitro properties of MSC may serve to optimize this strategy and predict in-vivo efficacy.

Funding

  • Other NIH Support