Skeletal Muscle-Derived Stem/Progenitor Cells: A Potential Strategy for the Treatment of Acute Kidney Injury.

Egle Pavyde,Neringa Sutkeviciene,Romaldas Maciulaitis,Arvydas Usas,Edgaras Stankevicius,Ernesta Ivanauskaite Didziokiene,Mykolas Mauricas,Arvydas Laurinavicius,Justinas Maciulaitis,Gintaras Sudzius

doi:10.1155/2016/9618480

Abstract

Skeletal muscle-derived stem/progenitor cells (MDSPCs) have been thoroughly investigated and already used in preclinical studies. However, therapeutic potential of MDSPCs isolated using preplate isolation technique for acute kidney injury (AKI) has not been evaluated. We aimed to characterize rat MDSPCs, compare them with bone marrow mesenchymal stem cells (BM-MSCs), and evaluate the feasibility of MDSPCs therapy for gentamicin-induced AKI in rats. We have isolated and characterized rat MDSPCs and BM-MSCs. Characteristics of rat BM-MSCs and MDSPCs were assessed by population doubling time, flow cytometry, immunofluorescence staining, RT-PCR, and multipotent differentiation capacity. Gentamicin-induced AKI model in rat was used to examine MDSPCs therapeutic effect. Physiological and histological kidney parameters were determined. MDSPCs exhibited similar immunophenotype, stem cell gene expression, and multilineage differentiation capacities as BM-MSCs, but they demonstrated higher proliferation rate. Single intravenous MDSPCs injection accelerated functional and morphological kidney recovery, as reflected by significantly lower serum creatinine levels, renal injury score, higher urinary creatinine, and GFR levels. PKH-26-labeled MDSPCs were identified within renal cortex 1 and 2 weeks after cell administration, indicating MDSPCs capacity to migrate and populate renal tissue. In conclusion, MDSPCs are capable of mediating functional and histological kidney recovery and can be considered as potential strategy for AKI treatment.

Highlights

Acute kidney injury (AKI) is a serious and frequent clinical condition with a high mortality rate [1]
The results of the present study indicate that rat muscle-derived stem/progenitor cells (MDSPCs) and BM-Mesenchymal stem cells (MSCs) have very similar immunophenotype, gene expression, and multilineage differentiation potential
The population doubling time (PDT) of MDSPCs appeared to be significantly lower than the PDT of the bone marrow mesenchymal stem cells (BM-MSCs), demonstrating the advantage of MDSPCs having a more rapid proliferation rate

Summary

Introduction

Acute kidney injury (AKI) is a serious and frequent clinical condition with a high mortality rate [1]. The incidence of this life-threatening complication is rapidly increasing, especially among critically ill hospitalized patients and among those undergoing major surgical procedures [1,2,3]. The main treatment options for AKI include supportive care and renal replacement therapy. Despite the application of renal replacement therapy for AKI patients, the mortality rates remain as high as 50–60% [1]. During the last several decades, the growing attention is drawn to the possible application of cellular therapies for the treatment of AKI

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