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Published on: September 18, 2017
Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular Disease
Ahmed Saad1, Allan B Dietz2, Sandra M S Herrmann1
1Divisions of *Nephrology and Hypertension and.
Abstract:
Atherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (n=14) received a single infusion of MSC (1.0 × 105 or 2.5 × 105 cells/kg; n=7 each) plus standardized medical treatment; the medical treatment only group (n=14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level-dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8-185.5 ml/min, P=0.01); contralateral kidney RBF increased (212.7-271.8 ml/min, P=0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%-17.8%] to 6.8% [interquartile range, 1.8%-12.9%], P=0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (-3% versus -24%, P=0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.
Insights
Adding mesenchymal stem cells (MSCs) to standard treatment improved renal blood flow and oxygenation in patients with renovascular disease (RVD). This first-in-human study showed MSC infusions were safe and beneficial for poststenotic kidneys.
Area of Science:
- Nephrology
- Regenerative Medicine
- Cardiovascular Research
Background:
- Atherosclerotic renovascular disease (RVD) impairs renal blood flow (RBF) and glomerular filtration rate (GFR), leading to kidney injury.
- Mesenchymal stem cells (MSCs) show preclinical promise in promoting angiogenesis and modulating immune responses in RVD models.
Purpose of the Study:
- To assess the safety and efficacy of intra-arterial autologous adipose-derived MSCs in patients with RVD, as an adjunct to standard medical treatment without revascularization.
- To evaluate the impact of MSC infusion on renal tissue oxygenation, perfusion, and GFR in the poststenotic kidney (STK).
Main Methods:
- A single-arm, dose-escalation study involving intra-arterial infusion of MSCs (1.0 × 10^5 or 2.5 × 10^5 cells/kg) into the STK of 14 patients with RVD.
- A control group (n=14) received only standardized medical treatment, matched for age, kidney function, and stenosis severity.
- Measurements included cortical and medullary volumes, RBF, GFR (iothalamate clearance), and tissue oxygenation (blood oxygen-level-dependent MRI).
Main Results:
- MSC infusions were well-tolerated. Three months post-infusion, STK cortical perfusion and RBF increased significantly (P=0.01).
- Renal hypoxia in the STK decreased (P=0.04), and contralateral kidney RBF also increased (P=0.01).
- Single-kidney GFR remained stable in the MSC group, whereas it declined in the medical treatment-only group (P=0.04).
Conclusions:
- Intra-arterial autologous MSC infusion is safe in patients with RVD.
- MSC treatment, without revascularization, improved renal tissue oxygenation and cortical blood flow in the STK.
- This study provides initial evidence for the therapeutic potential of MSCs in managing RVD-associated kidney injury.

