Preclinical Experimental Applications of miRNA Loaded BMSC Extracellular Vesicles

Çetin, Zafer; Saygılı, Eyüp İlker; Görgişen, Gökhan; Sokullu, Emel

doi:10.1007/s12015-020-10082-x

Cited by 14 publications

(11 citation statements)

References 154 publications

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“…miRNAs exert their biological functions through the downregulation of gene expression via translational repression or degradation of mRNA targets ( 8 , 9 ). As per recent reports, multiple miRNAs could potentially play a part in osteogenesis ( 10 – 12 ). Several studies indicated the potential roles of miRNAs in osteoporosis pathogenesis, affecting BMSC osteogenic differentiation ( 13 – 16 ).…”

Section: Introductionsupporting

confidence: 53%

The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression

et al. 2021

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Osteoporosis is a complex multifactorial disorder linked to various risk factors and medical conditions. Bone marrow-derived mesenchymal stem cell (BMSC) dysfunction potentially plays a critical role in osteoporosis pathogenesis. Herein, the study identified that miR-4739 was upregulated in BMSC cultures harvested from osteoporotic subjects. BMSCs were isolated from normal and osteoporotic bone marrow tissues and identified for their osteogenic differentiation potential. In osteoporotic BMSCs, miR-4739 overexpression significantly inhibited cell viability, osteoblast differentiation, mineralized nodule formation, and heterotopic bone formation, whereas miR-4739 inhibition exerted opposite effects. Through direct binding, miR-4739 inhibited distal-less homeobox 3 (DLX3) expression. In osteoporotic BMSCs, DLX3 knockdown also inhibited BMSC viability and osteogenic differentiation. Moreover, DLX3 knockdown partially attenuated the effects of miR-4739 inhibition upon BMSCs. Altogether, the miR-4739/DLX3 axis modulates the capacity of BMSCs to differentiate into osteoblasts, which potentially plays a role in osteoporosis pathogenesis. The in vivo and clinical functions of the miR-4739/DLX3 axis require further investigation.

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Section: Introductionsupporting

confidence: 53%

The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression

et al. 2021

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“…Many studies have proven that BMSCs can produce miRNAs (Cetin et al, 2021). Feng et al demonstrated that MSC-derived miRNAs reduced infarct size and cardiac fibrosis by inhibiting apoptosis in mice with myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid Combined With Bone Marrow Mesenchymal Stem Cells Attenuates the Activation of Hepatic Stellate Cells and Alleviates Liver Fibrosis

Zhang

Jiang

et al. 2022

Front. Pharmacol.

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Bone marrow mesenchymal stem cells (BMSCs) can effectively alleviate liver fibrosis, but the efficacy of cell therapy alone is insufficient. In recent years, a combination of traditional Chinese medicine (TCM) and cell therapy has been increasingly used to treat diseases in clinical trials. Ferulic acid (FA) is highly effective in treating liver fibrosis, and a combination of cells and drugs is being tested in clinical trials. Therefore, we combined BMSCs and Ferulic acid to treat CCl4-induced fibrosis and determine whether this combination was more effective than single treatment. We used BMSCs and FA to treat CCl4-induced fibrosis in rat models, observed their therapeutic effects, and investigated the specific mechanism of this combination therapy in liver fibrosis. We created a BMSC/hepatic stellate cell (HSC) coculture system and used FA to treat activated HSCs to verify the specific mechanism. Then, we used cytochalasin D and angiotensin II to investigate whether BMSCs and FA inactivate HSCs through cytoskeletal rearrangement. MiR-19b-3p was enriched in BMSCs and targeted TGF-β receptor II (TGF-βR2). We separately transfected miR-19b-3p into HSCs and BMSCs and detected hepatic stellate cell activation. We found that the expression of the profibrotic markers α-SMA and COL1-A1 was significantly decreased in the combination group of rats. α-SMA and COL1-A1 levels were also significantly decreased in the HSCs with the combination treatment. Cytoskeletal rearrangement of HSCs was inhibited in the combination group, and RhoA/ROCK pathway gene expression was decreased. Following angiotensin II treatment, COL1-A1 and α-SMA expression increased, while with cytochalasin D treatment, profibrotic gene expression decreased in HSCs. The expression of COL1-A1, α-SMA and RhoA/ROCK pathway genes was decreased in the activated HSCs treated with a miR-19b-3p mimic, indicating that miR-19b-3p inactivated HSCs by suppressing RhoA/ROCK signalling. In contrast, profibrotic gene expression was significantly decreased in the BMSCs treated with the miR-19b-3p mimic and FA or a miR-19b-3p inhibitor and FA compared with the BMSCs treated with the miR-19b-3p mimic alone. In conclusion, the combination therapy had better effects than FA or BMSCs alone. BMSC and FA treatment attenuated HSC activation and liver fibrosis by inhibiting cytoskeletal rearrangement and delivering miR-19b-3p to activated HSCs, inactivating RhoA/ROCK signalling. FA-based combination therapy showed better inhibitory effects on HSC activation.

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“…Therefore, modifiable BMSC-EVs may represent a safer and more promising therapeutic strategy. In recent years, BMSC-EVs have been gradually applied in bone disease research as a nanocarrier [ 28 ]. Numerous studies have shown that BMSC-EVs can promote osteogenesis, angiogenesis and bone mineralization, suggesting that BMSC-EV-based cell-free therapy is a promising strategy for bone regeneration and repair [ 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of BMSC-Derived EVs on Bone Metabolism

et al. 2022

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Extracellular vesicles (EVs) are small membrane vesicles that can be secreted by most cells. EVs can be released into the extracellular environment through exocytosis, transporting endogenous cargo (proteins, lipids, RNAs, etc.) to target cells and thereby triggering the release of these biomolecules and participating in various physiological and pathological processes. Among them, EVs derived from bone marrow mesenchymal stem cells (BMSC-EVs) have similar therapeutic effects to BMSCs, including repairing damaged tissues, inhibiting macrophage polarization and promoting angiogenesis. In addition, BMSC-EVs, as efficient and feasible natural nanocarriers for drug delivery, have the advantages of low immunogenicity, no ethical controversy, good stability and easy storage, thus providing a promising therapeutic strategy for many diseases. In particular, BMSC-EVs show great potential in the treatment of bone metabolic diseases. This article reviews the mechanism of BMSC-EVs in bone formation and bone resorption, which provides new insights for future research on therapeutic strategies for bone metabolic diseases.

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Preclinical Experimental Applications of miRNA Loaded BMSC Extracellular Vesicles

Cited by 14 publications

References 154 publications

The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression

The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression

Ferulic Acid Combined With Bone Marrow Mesenchymal Stem Cells Attenuates the Activation of Hepatic Stellate Cells and Alleviates Liver Fibrosis

Effects of BMSC-Derived EVs on Bone Metabolism

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