Comparative restoration of acute liver failure by menstrual blood stem cells compared with bone marrow stem cells in mice model MINA FATHI-KAZEROONI 1 , GHOLAMREZA TAVOOSIDANA 1 , MASOUD TAGHIZADEH-JAHED 2 , SAYEH KHANJANI 2 , HANANEH GOLSHAHI 3 , CAROLINE E. GARGETT 4 , HALEH EDALATKHAH 2 & SOMAIEH KAZEMNEJAD 2 1 Department of Molecular Medicine, School of AdvancedTechnologies in Medicine,Tehran University of Medical Sciences,Tehran, Iran, 2 Reproductive Biotechnology Research Center,Avicenna Research Institute,ACECR,Tehran, Iran, 3 Department of Pathology, Faculty ofVeterinary Medicine, University ofTehran,Tehran, Iran, and 4 The Ritchie Centre, Hudson Institute of Medical Research, and Department of Obstetrics and Gynaecology, Monash University, Melbourne,Victoria, Australia Abstract Background aims. The application of menstrual blood stem cells (MenSCs) in regenerative medicine is gaining increasing attention. The aim of this study was to investigate the therapeutic potential of MenSCs compared with bone marrow– derived stem cells (BMSCs) in an animal model of CCl4-induced acute hepatic failure. Methods. Injured Balb/C mice were divided into multiple groups and received MenSCs, BMSCs or hepatocyte progenitor-like (HPL) cells derived from these cells. Results. Tracking of green fluorescent protein–labeled cells showed homing of cells in injured areas of the liver. In addition, the liver engraftment of MenSCs was shown by immunofluorescence staining using anti-human mitochondrial antibody. Microscopically examination, periodic acid-Schiff and Masson’s trichrome staining of liver sections demon- strated the considerable liver regeneration post–cell therapy in all groups. Assessment of serum parameters including aspartate aminotransferase, alanine aminotransferase, total bilirubin, urea and cholesterol at day 7 exhibited significant reduction, such that this downward trend continued significantly until day 30. The restoration of liver biochemical markers, changes in mRNA levels of hepatic markers and the suppression of inflammatory markers were more significant in the MenSC- treated group compared with the BMSC-treated group. On the other hand, HPL cells in reference to undifferentiated cells had better effectiveness in the treatment of the acute liver injury. Conclusions. Our data show that MenSCs may be con- sidered an appropriate alternative stem cell population to BMSCs for treatment of acute liver failure. Key Words: bone marrow stem cells, liver injury, menstrual blood stem cells, regenerative medicine Introduction The adult liver has a critical role in regulating many metabolic pathways [1]. Acute liver failure (ALF) is a life-threatening condition with a high mortality rate [2]. Many patients with liver failure require a lifesaving liver transplant but are faced with major limitations including long waiting lists, lack of donors, transplant rejection and high cost [3]. In recent years, bone marrow–derived stem cells (BMSCs) are the most common type of mesenchymal stromal cells (MSCs) used in cell therapy [4–6]. Several studies showed the potential of BMSCs in regenerative med- icine based on their multipotent, anti-apoptotic, immunosuppressive and paracrine properties [7,8]. Nevertheless, problems such as limited availability, invasive sample collection and low proliferation ca- pacity limit the applicability of BMSCs [9]. The recent identification of MSC-like cells in menstrual blood (MenSCs) provides a non-invasive source of MSCs with several advantages, such as easy accessi- bility without need for anaesthetic, renewability as they can be sourced on a monthly basis, high prolif- erative capacity in culture without inducing genetic abnormalities and lack of ethical concerns [10–13]. Moreover, immunomodulatory properties of MenSCs and their therapeutic potential in different diseases emphasize the safety and efficacy of their application for cell therapy [14–18]. Our group and others showed MenSCs can differentiate into multiple mesodermal and occasionally endodermal and ectodermal lin- eages [19], but with different capacities depending Correspondence: Somaieh Kazemnejad, PhD,Tissue Engineering Department, Biotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box 19615-1177,Tehran, Iran. E-mails: kazemnejad_s@yahoo.com, s.kazemnejad@avicenna.ac.ir ARTICLE IN PRESS (Received 17 March 2017; accepted 20 August 2017) ISSN 1465-3249 Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jcyt.2017.08.022 Cytotherapy, 2017; ■■: ■■–■■