Autologous mesenchymal stem cells increase cortical perfusion in renovascular disease

Ahmed Saad, Allan B Dietz, Sandra Herrmann, LaTonya Hickson, James Glockner, Michael A. McKusick, Sanjay Misra, Haraldur Bjarnason, Adam S. Armstrong, Dennis A. Gastineau, Lilach O Lerman, Stephen C Textor

Research output: Contribution to journalArticle

30 Citations (Scopus)

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-derivedMSCs into STK to standardized medical treatment in human subjectswithout revascularization. The intervention group (n=14) received a single infusion of MSC (1.0 3 105 or 2.5 3 105 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 andmedullary volumes, perfusion, and RBF usingmultidetector 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 (23% versus 224%, 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.

Original languageEnglish (US)
Pages (from-to)2777-2785
Number of pages9
JournalJournal of the American Society of Nephrology
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2017

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Mesenchymal Stromal Cells
Renal Circulation
Perfusion
Kidney
Iothalamic Acid
Therapeutics
Safety
Intra Arterial Infusions
Renal Artery
Pathologic Constriction
Tomography
Oxygen
Wounds and Injuries

ASJC Scopus subject areas

  • Nephrology

Cite this

Autologous mesenchymal stem cells increase cortical perfusion in renovascular disease. / Saad, Ahmed; Dietz, Allan B; Herrmann, Sandra; Hickson, LaTonya; Glockner, James; McKusick, Michael A.; Misra, Sanjay; Bjarnason, Haraldur; Armstrong, Adam S.; Gastineau, Dennis A.; Lerman, Lilach O; Textor, Stephen C.

In: Journal of the American Society of Nephrology, Vol. 28, No. 9, 01.09.2017, p. 2777-2785.

Research output: Contribution to journalArticle

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