Abstract: SA-OR100

Autologous Mesenchymal Stem Cells Decrease Blood Pressure and Kidney Injury in Human Renovascular Disease

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Saad, Ahmed, Mayo Clinic, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo Clinic, Rochester, Minnesota, United States
  • Glockner, James, 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

Atherosclerotic renovascular disease (RVD) reduces blood flow (RBF), glomerular filtration rate (GFR) and accelerates both systemic hypertension and post-stenotic kidney (SK) tissue injury. Preclinical studies indicate that MSCs stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and clinical effects of intrarenal autologous MSCs in a phase 1/2A study of human subjects with RVD.

Methods

Adipose tissue-derived MSCs were collected from 21 RVD patients (age 73.7 ± 4.3; 13 male and 8 females). Inpatient studies were performed during fixed Na+ intake and ACE/ARB Rx before and 3 months after unilateral intra-arterial single infusion of MSC of either 1.0, 2.5 or 5 x 10^5 cells/kg into the SK (n=7 each). SK cortical/medullary perfusion and RBF were measured using multidetector CT, GFR by iothalamate clearance, Injury markers including NGAL and VEGF-C were measured in the renal veins and renal tissue oxygenation was assessed by BOLD-MRI at 3T.

Results

Intra-arterial MSC infusions were tolerated without adverse effects. Tissue perfusion and RBF increased after 3 months (p<0.05 vs. baseline), and fractional hypoxia (%R2*>30 sec-1) decreased in the treated kidneys. Renal vein levels of NGAL and VEGF-C decreased (Table). Systolic blood pressure fell (P<0.05) and iothalamate-GFR marginally increased (P=0.053) 3 months after MSC (Table). These changes were of similar magnitude among the 3 doses.

Conclusion

In this “first-in-human” dose escalation study in 21 patients with atherosclerotic RVD, a single intraarterial infusion of autologous adipose tissue-derived MSCs into the SK decreased systolic blood pressure and increased RBF after three months. These were associated with a reduction in tissue hypoxia and renal injury cytokines, while GFR tended to improve. Our results demonstrate the capability of intrarenal MSC to increase tissue oxygenation and RBF in the human kidney, and support a potential role for MSC in the management of ischemic renal disease.

Funding

  • NIDDK Support