Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway

Shen, Xinghai; Pan, Bo; Zhou, Hui‐Ming; Liu, Lingjuan; Lv, Tiewei; Zhu, Jing; Huang, Xupei; Tian, Jie

doi:10.1186/s12929-017-0337-9

Cited by 58 publications

(54 citation statements)

References 33 publications

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“…In recent years, MSC have also been utilized for the generation of mesenchymal as well as non-mesenchymal cell lineages, including neuron-like, hepatocyte-like, and cardiac-like cells [6][7][8][9][10]. Despite these promising results, the differentiation of human MSC into fully mature cardiomyocytes bearing all their respective phenotypical and functional characteristics is difficult [11][12][13][14][15]. As MSC are located in various tissues, they represent a heterogeneous progenitor cell population dependent on the tissue source and the individual donor [16].…”

Section: Introductionmentioning

confidence: 99%

“…Small non-coding RNAs, like microRNAs (miRNA) and chemically modified messenger RNA (mRNAs) allow the manipulation of cell behavior for a limited period of time, e.g., triggering (trans)-differentiation by activation of lineage-specific molecular pathways. Some studies have already shown that alteration of gene expression using selected miRNAs can induce cardiac differentiation of MSC to a small extent [15,25,26], while data about mRNA-based cardiac reprogramming is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Mueller

Wolfien

Ekat

et al. 2020

Cells

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“…MicroRNA (miRNA or miR) is a class of small non-encoding RNA molecules (18)(19)(20)(21)(22) nucleotides) that bind with the 3'-untranslated region (UTR) of mRNA to inhibit its translation (15). miRNA plays important regulatory roles in post-transcriptional levels of genes, and widely participates in the proliferation, aging, apoptosis, migration, differentiation, and drug resistance of cells (16).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, miR-33b-5p enhances the sensitivity of gastric cancer cells to chemotherapeutic drugs and improves their clinical efficacy (19). Of note, Wnt/β-catenin signaling pathway that is regulated by Dact2, is also regulated by various miRNA molecules (20). Therefore, miRNA is likely to be involved in the regulation of Dact2 gene.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑214 promotes the proliferation, migration and invasion of gastric cancer MKN28 cells by suppressing the expression of Dact2

Zhao

Fan

et al. 2018

Exp Ther Med

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The present study examined the expression of Dapper, antagonist of β-catenin 2 (Dact2) and microRNA (miR)-214 in gastric cancer at tissue and cellular levels, and to understand their biological roles. A total of 42 gastric cancer patients were enrolled in the present study. Bioinformatics tool was used to predict the miR molecule that potentially regulates Dact2 expression. To measure the expression of miR-214 and Dact2, reverse transcription-quantitative polymerase chain reaction was employed. Mixed gastric adenocarcinoma type MKN28 cells were transfected with negative control (NC), miR-214 mimics or inhibitor. The CCK-8 assay was used to investigate the proliferation of mixed gastric adenocarcinoma type MKN28 cells. To study migration and invasion abilities of mixed gastric adenocarcinoma type MKN28 cells, the Transwell assay was performed. To determine the expression of Dact2 protein, western blotting was conducted and the rescue assay was utilized to study the biological roles of miR-214 and Dact2 in mixed gastric adenocarcinoma type MKN28 cells. To test whether Dact2 is a direct target of miR-214, the dual luciferase reporter assay was performed. Results indicated that the expression of miR-214 was elevated, but expression of Dact2 mRNA was decreased in gastric cancer tissues, which was closely correlated with the invasion, metastasis, occurrence and development of gastric cancer. Notably, miR-214 promoted the proliferation of mixed gastric adenocarcinoma type MKN28 cells in vitro, whereas but Dact2 inhibited the proliferation of these cells. Downregulation of miR-214 expression or upregulation of Dact2 expression inhibited the migration and invasion of mixed gastric adenocarcinoma type MKN28 cells. Furthermore, miR-214 regulated the expression of Dact2 protein and its downstream β-catenin protein in mixed gastric adenocarcinoma type MKN28 cells. Dact2 reversed the effect of miR-214 on the proliferation, migration and invasion of mixed gastric adenocarcinoma type MKN28 cells. In addition, miR-214 directly targeted the 3'-UTR seeding region of Dact2 mRNA to regulate its expression. The present study demonstrated that expression of miR-214 was upregulated in gastric cancer tissues, and positively correlated with lymphatic metastasis and clinical staging. In addition, expression of Dact2 was downregulated in gastric cancer tissues and negatively correlated with lymphatic metastasis and clinical staging. Notably, the present findings suggest that miR-214 promoted the proliferation, migration and invasion of mixed gastric adenocarcinoma type MKN28 cells by suppressing the expression of Dact2.

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“…MiRs have also been proven to be important translational determinants of the SC fate [507]. A combination of 5-azacytine and miR-1 overexpression induces the expression of cardiac specific genes like Nkx2.5 and troponin I via activation of the Wnt/β-catenin signaling pathway in MSCs [508,509]. In addition, miR-133a and miR-499 were shown to promote the commitment of MSCs and CSCs/CPCs towards a cardiomyogenic lineage [510][511][512][513].…”

Section: Genetic Sc Modificationsmentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

174

140

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A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

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Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway

Cited by 58 publications

References 33 publications

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

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

MicroRNA‑214 promotes the proliferation, migration and invasion of gastric cancer MKN28 cells by suppressing the expression of Dact2

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

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