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World J Stem Cells. Nov 26, 2014; 6(5): 644-650
Published online Nov 26, 2014. doi: 10.4252/wjsc.v6.i5.644
Potential advantages of acute kidney injury management by mesenchymal stem cells
Francesca Bianchi, Elisa Sala, Chiara Donadei, Irene Capelli, Gaetano La Manna
Francesca Bianchi, Laboratory of Molecular Biology and Stem Cell Engineering - National Institute of Biostructures and Biosystems, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Elisa Sala, Chiara Donadei, Irene Capelli, Gaetano La Manna, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, 40128 Bologna, Italy
Author contributions: Bianchi F, Sala E, Donadei C, Capelli I and La Manna G wrote the paper.
Correspondence to: Gaetano La Manna, MD, PhD, Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, Via Zamboni, 33, 40128 Bologna, Italy. gaetano.lamanna@unibo.it
Telephone: +39-051-6364577 Fax: +39-051-344439
Received: July 28, 2014
Revised: September 8, 2014
Accepted: September 16, 2014
Published online: November 26, 2014
Processing time: 61 Days and 16.8 Hours
Abstract

Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury (AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells (MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.

Keywords: Mesenchymal stem cells; Paracrine; Soluble factors; Microvesicle; Acute kidney injury; Regenerative medicine; Preclinical; Clinical trial

Core tip: Mesenchymal stem cells (MSCs) may have an important therapeutic potential in acute kidney injury management. A body of evidence has demonstrated that MSCs act through a paracrine/endocrine secretion of soluble factors and microvesicles. We summarize preclinical studies and ongoing clinical trials that evaluate the role of MSCs in restoring kidney function. We critically explain the current concerns about the use of MSCs and microvesicles that limit their applications in clinical trials. Then, we propose the future directions that could lead to extend MSCs use in humans.