Transplantation of Umbilical Cord-Derived Mesenchymal Stem Cells Overexpressing Lipocalin 2 Ameliorates Ischemia-Induced

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Transplantation of Umbilical Cord-Derived Mesenchymal Stem Cells Overexpressing Lipocalin 2 Ameliorates Ischemia-Induced Injury and Reduces Apoptotic Death in a Rat Acute Myocardial Infarction Model Zahra Alijani-Ghazyani 1 & Reza Sabzevari 1 & Amaneh Mohammadi Roushandeh 1,2 & Ali Jahanian-Najafabadi 3 & Fatemeh Amiri 4 & Mehryar Habibi Roudkenar 5

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Myocardial infarction (MI) is a leading cause of death worldwide and requires development of efficient therapeutic strategies . Mesenchymal stem cells (MSCs) -based therapy of MI has been promising but inefficient due to undesirable microenvironment of the infarct tissue. Hence, the current study was conducted to fortify MSCs against the unfavorable microenvironment of infarct tissue via overexpression of Lipocalin 2 (Lcn2) as a cytoprotective factor. The engineered cells (Lcn2-MSCs) were transplanted to infarcted heart of a rat model of MI. According to our findings, Lcn2 overexpression resulted in increased MSCs survival in the MI tissue (p < 0.05) compared to non-engineered cells. Furthermore, the infusion of Lcn2-MSCs mitigated Left ventricle (LV) remodeling, decreased fibrosis (p < 0.0001), and reduced apoptotic death of the LVs’ cells (p < 0.0001) compared to the control. Our findings suggest a potential novel therapeutic strategy for MI, however, further investigations such as safety and efficacy assessments in large animals followed by clinical trials are required. Keywords Myocardial infarction . Mesenchymal stem cells . Lipocalin 2 . Apoptosis . Exogenous expression

Introduction Development of efficient therapeutic strategies for myocardial infarction (MI) is necessary since it is the leading cause of deaths and disabilities worldwide. Loss of cardiomyocytes and inability of the myocardium to self-

* Mehryar Habibi Roudkenar [email protected] 1

Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran

2

Anatomical Sciences Department, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran

3

Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

4

Department of Medical Laboratory Science, Paramedicine Faculty, Hamadan University of Medical Science, Hamadan, Iran

5

Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

regenerate following MI lead to permanent heart failure [1–3]. Therefore, novel therapeutic approaches to restore cardiomyocytes and their function after MI have always been investigated by both basic and clinical scientists. One of the novel approaches for recovery of infarcted tissue function is transplantation of mesenchymal stem cells (MSCs) [4–8], and several preclinical and clinical studies have been conducted in this regard [9–12]. MSCs are capable of homing and engrafting into damaged tissu