Journal of cell signaling, Volume (3), No (3), Year (2018-9) , Pages (188-189)

Title : ( Transduced Mesenchymal Stem Cells and Cardiomyogenic Differentiation )

Authors: Vajiheh Neshati , Bibi Sedigheh Fazly Bazzaz , Majid Mojarrad , Zeinab Neshati , Mohammad Amin Kerachian ,

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ublished article in which we showed the overexpression of Tbx20 induced cardiomyogenic differentiation in adipose-derived mesenchymal stem cells (ADMSCs) [1]. Myocardial infarction (MI), a main reason of mortality in the world, occurs due to death of cardiac cells following cardiac ischemic diseases. Since the adult mammalian cardiomyocytes are unable to regenerate and repair damaged tissues, constant cell loss leads to failure of contractile tissue, which reduces cardiac output and function [2]. Producing new cardiomyocytes to improve the function of the infarcted heart is the main purpose of cardiac regenerative medicine. In this regard, stem cells therapy has been determined as one of the most potential therapeutic options by replacing the damaged heart cells with new cardiomyocytes [3]. Mesenchymal stem cells (MSCs) with several specific features are one of the most favourable candidates for regenerative cardiac therapies. They are multipotent stromal cells with self-renewal capacity that can differentiate into a variety of cells. Human MSCs can be obtained in large amounts and are significantly expanded in vitro without losing their normal karyotype and undergoing senility [4,5]. Among MSCs, ADMSCs are seemingly the proper candidates for tissue regeneration and organ repair due to the ease of isolation and development in ex vivo [6-8]. There is substantial data supporting the fact that ADMSCs have the ability to differentiate into cardiomyocytes [8-12] and exhibit greater cardiomyogenic potential than other sources of MSCs [13]. Improving the myoregenerative potential of MSCs depends on the recognition of molecular mediators and transcription factors that regulate cardiac lineage-specific genes during heart development and cardiomyogenic differentiation. Many researchers have attempted to introduce and overexpress cardiomyogenic factors into stem cells. Overexpression of cardiomyogenic transcription factors have been used for differentiation of several types of MSCs into cardiomyocytes [14-18]. Despite the constant progress and innovation in gene transfer to target cells, there are some limitations in clinical success of gene therapy that is due to the lack of a safe and highly efficient gene delivery system, offtarget transduction and genotoxicity. Lentiviral vectors (LVs) are relatively suitable candidates for gene delivery into MSCs [19,20], since they have the capability to induce constant expression of transgene into target cells, with low cytotoxicity and limited immunogenicity [21,22]. In our recent study, cardiomyogenic effects of Tbx20 overexpression in ADMSCs were evaluated. To this end, ADMSCs were transduced with lentiviral vectors encoding Tbx20 and cardiomyogenic differentiation was investigated 7 and 14 days post-transduction. The transduced cells adopted a myocyte-like shape and increased the expression of the cardiomyogenic differentiation markers. These findings elucidated that targeted efficient expression of Tbx20 in ADMSCs can generate cardiomyocyte-like cells [1]. Tbx20 is initially expressed in cardiac progenitor cells and has a key regulatory role during heart development and maturation [23-26]. The main question that arises here is that, by which mechanism(s) Tbx20 overexpression can result in cardiomyogenic differentiation of ADMSCs? It is known that Tbx20 interacts with various cardiac transcription factors such as Nkx2-5, GATA4 and GATA5 and promotes the expression of genes like connexin 40, connexin 43, Mef2c and Nkx2.5 which are crucial for cardiomyocyte differentiation [23,27-31]. Our findings are the initial steps of cardiomyogenesis using Tbx20-transduced ADMSCs. To achieve a complete cardiomyogenic reprogramming, combination of several cardiac factors is required. In addition to the genetic modification, pre-conditioning and exposing the ADMSCs to additional cardiomyogenic stimuli such as growth factors, extracellular matrix components, electrical stimulation and cocultures with cardiomyocytes can be useful. The future plan would be preclinical efficacy studies, to aim efficiency and safety concerns prior to clinical trials.


Transduced Mesenchymal Stem Cells and Cardiomyogenic Differentiation
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author = {Vajiheh Neshati and Bibi Sedigheh Fazly Bazzaz and Majid Mojarrad and Neshati, Zeinab and Mohammad Amin Kerachian},
title = {Transduced Mesenchymal Stem Cells and Cardiomyogenic Differentiation},
journal = {Journal of cell signaling},
year = {2018},
volume = {3},
number = {3},
month = {September},
issn = {2576-1471},
pages = {188--189},
numpages = {1},
keywords = {Transduced Mesenchymal Stem Cells and Cardiomyogenic Differentiation},


%0 Journal Article
%T Transduced Mesenchymal Stem Cells and Cardiomyogenic Differentiation
%A Vajiheh Neshati
%A Bibi Sedigheh Fazly Bazzaz
%A Majid Mojarrad
%A Neshati, Zeinab
%A Mohammad Amin Kerachian
%J Journal of cell signaling
%@ 2576-1471
%D 2018