MicroRNA-499a-5p Promotes Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to Cardiomyocytes

Neshati, Vajiheh; Mollazadeh, Samaneh; Bazzaz, Bibi Sedigheh Fazly; Vries, Antoine A.F. de; Mojarrad, Majid; Naderi‐Meshkin, Hojjat; Neshati, Zeinab; Mirahmadi, Mahdi; Kerachian, Mohammad Amin

doi:10.1007/s12010-018-2734-2

Cited by 26 publications

(18 citation statements)

References 29 publications

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“…MSCs have been manipulated in vitro to alter the expression of various myo-miRs (myocardium-related miRs) including miR-1, miR-133, miR-208, and miR-499 to enhance their cardiac differentiation [98][99][100]. A recent study has explored an interesting aspect of myo-miRs regarding their exosome-encapsulated release from the infarcted heart (except for miR-133 which is partially released in the exosomes) that gets transferred to the BM mononuclear cells [101].…”

Section: Manipulation Of Mscs To Enhance Exosomal Mir Payloadmentioning

confidence: 99%

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

2020

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Bone marrow-derived mesenchymal stem cells (MSCs) have successfully progressed to phase III clinical trials successive to an intensive in vitro and pre-clinical assessment in experimental animal models of ischemic myocardial injury. With scanty evidence regarding their cardiogenic differentiation in the recipient patients' hearts post-engraftment, paracrine secretion of bioactive molecules is being accepted as the most probable underlying mechanism to interpret the beneficial effects of cell therapy. Secretion of small non-coding microRNA (miR) constitutes an integral part of the paracrine activity of stem cells, and there is emerging interest in miRs' delivery to the heart as part of cell-free therapy to exploit their integral role in various cellular processes. MSCs also release membrane vesicles of diverse sizes loaded with a wide array of miRs as part of their paracrine secretions primarily for intercellular communication and to shuttle genetic material. Exosomes can also be loaded with miRs of interest for delivery to the organs of interest including the heart, and hence, exosome-based cell-free therapy is being assessed for cell-free therapy as an alternative to cell-based therapy. This review of literature provides an update on cell-free therapy with primary focus on exosomes derived from BM-derived MSCs for myocardial repair.

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Section: Manipulation Of Mscs To Enhance Exosomal Mir Payloadmentioning

confidence: 99%

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

2020

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“…This might be attributed to the fact that the miRNA concentrations used in this study are not sufficient to significantly increase the expression level of cardiac-specific genes, although uptake efficiency for miRNA was about 80%. In this regard, some studies have used viral vectors to ensure constitutive overexpression of miRNA [25,64]. Given that miRNAs have a very short half live, transient transfection approaches, as used in our study, might be less effective.…”

Section: Discussionmentioning

confidence: 98%

“…Myo-miRNA based programming has been successfully applied for the conversion of cardiac fibroblasts, into cardiomyocytes [36]. For MSCs, cardiac induction by miRNA is less efficient as shown by different groups [25,63,64]. For example, it was demonstrated that transfection with miRNA-1-2 promote the expression of GATA4, NKX2.5 and cardiac Troponin in BM MSCs [15].…”

Section: Discussionmentioning

confidence: 99%

RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells

Mueller

Wolfien

Ekat

et al. 2020

Cells

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Multipotent adult mesenchymal stromal cells (MSCs) could represent an elegant source for the generation of patient-specific cardiomyocytes needed for regenerative medicine, cardiovascular research, and pharmacological studies. However, the differentiation of adult MSC into a cardiac lineage is challenging compared to embryonic stem cells or induced pluripotent stem cells. Here we used non-integrative methods, including microRNA and mRNA, for cardiac reprogramming of adult MSC derived from bone marrow, dental follicle, and adipose tissue. We found that MSC derived from adipose tissue can partly be reprogrammed into the cardiac lineage by transient overexpression of GATA4, TBX5, MEF2C, and MESP1, while cells isolated from bone marrow, and dental follicle exhibit only weak reprogramming efficiency. qRT-PCR and transcriptomic analysis revealed activation of a cardiac-specific gene program and up-regulation of genes known to promote cardiac development. Although we did not observe the formation of fully mature cardiomyocytes, our data suggests that adult MSC have the capability to acquire a cardiac-like phenotype when treated with mRNA coding for transcription factors that regulate heart development. Yet, further optimization of the reprogramming process is mandatory to increase the reprogramming efficiency.

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“…Asymptomatic carotid stenosis [63], cardiac amyloidosis [150], heart failure [151], atherosclerosis [152,153], aortic stenosis [154], acute myocardial infarction [155], acute ischemic stroke [156], focal cerebral ischemia [157], pulmonary artery hypertension [158], obesity [159] hsa-miR-342-3p 14q32.2 Cardiac amyloidosis [150], obesity [160], T1DM [52,149,161], T2DM [149,162,163], GDM [149], endothelial dysfunction [164] hsa-miR-499a-5p 20q11. 22 Myocardial infarction [17,165], hypoxia [166], cardiac regeneration [167], vascular endothelial dysfunction [15] hsa-miR-574-3p 4p14 Myocardial infarction [168], coronary artery disease [100], cardiac amyloidosis [150], stroke [169], T2DM [104,170]…”

Section: Introductionmentioning

confidence: 99%

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases

Hromadníková

Dvořáková

Krofta

2020

IJMS

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Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3–11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p < 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.

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MicroRNA-499a-5p Promotes Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to Cardiomyocytes

Cited by 26 publications

References 29 publications

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases

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