Sox2 Suppression by miR-21 Governs Human Mesenchymal Stem Cell Properties

Trohatou, Ourania; Zagoura, Dimitra; Bitsika, Vasiliki; Pappa, Kalliopi I.; Antsaklis, A.; Anagnou, Nicholas P.; Roubelakis, Maria G.

doi:10.5966/sctm.2013-0081

Cited by 71 publications

(60 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results were in agreement with the following reports. Trohatou et al 25 revealed that overexpression of miR-21 could accelerate osteogenesis and impair adipogenesis in hBMMSCs, and Yang et al 34 validated that miR-21 could promote the osteoblast differentiation of hMMSCs by repressing SPRY1, which can negatively regulate the osteogenic differentiation of MSCs. Meng et al 35 also found that miR-21 could promote the osteogenic differentiation of human umbilical cord mesenchymal stem cells through the PI3K-AKT-GSK3β pathway via the stabilization and accumulation of β-catenin.…”

mentioning

confidence: 99%

“…As one of the most studied miRNAs, miR-21 plays a general role in regulating a variety of physiological and pathological processes. 25,26 Studies of embryonic stem cells and mesenchymal stem cells (MSCs) have shown that the levels of miR-21 increased substantially following the induction of differentiation, indicating that miR-21 might play important roles in stem cell differentiation and development. 27 Among these roles, miR-21 was found to suppress stemness maintenance by downregulating SOX2 expression and promoting the osteogenic differentiation of hMSCs.…”

mentioning

confidence: 99%

“…27 Among these roles, miR-21 was found to suppress stemness maintenance by downregulating SOX2 expression and promoting the osteogenic differentiation of hMSCs. 25 To find a safe and efficient vector for gene delivery, we developed a CS/HA nanocarrier system as a nonviral vector for reverse transfection. 15 CS possesses good biocompatibility and biodegradability, but a single application of CS lacks stability due to its low water solubility at physiological pH, so CS likely could not protect miRNA efficiently, leading to the release of a large amount of miRNA before being endocytosed by the cells.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Wang

Wu²,

Wei

et al. 2016

IJN

View full text Add to dashboard Cite

Cell sheet engineering has emerged as a novel approach to effectively deliver seeding cells for tissue regeneration, and developing human bone marrow mesenchymal stem cell (hBMMSC) sheets with high osteogenic ability is a constant requirement from clinics for faster and higher-quality bone formation. In this work, we fabricated biocompatible and safe chitosan (CS)/hyaluronic acid (HA) nanoparticles (NPs) to deliver microRNA-21 (miR-21), which has been proved to accelerate osteogenesis in hBMMSCs; then, the CS/HA/miR-21 NPs were cross-linked onto the surfaces of culture plates with 0.2% gel solution to fabricate miR-21-functionalized culture plates for reverse transfection. hBMMSC sheets were induced continuously for 14 days using a vitamin C-rich method on the miR-21-functionalized culture plates. For the characterization of CS/HA/miR-21 NPs, the particle size, zeta potential, surface morphology, and gel retardation were sequentially investigated. Then, the biological effects of hBMMSC sheets on the miR-21-functionalized culture plates were evaluated. The assay results demonstrated that the hBMMSC sheets could be successfully induced via the novel reverse transfection approach, and miR-21 delivery significantly enhanced the in vitro osteogenic differentiation of hBMMSC sheets in terms of upregulating calcification-related gene expression and enhancing alkaline phosphatase production, collagen secretion, and mineralized nodule formation. The enhanced osteogenic activity of hBMMSC sheets might promisingly lead to more rapid and more robust bone regeneration for clinical use.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Wang

Wu²,

Wei

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…In that work two cellular populations were isolated from amniotic fluid: spindle-shaped (SS) and roundshaped (RS). Interestingly, induction of miR21 was found to accelerate osteogenesis more in the SS population than in RS cells [71] . Finally, human AFMSCs analyzed by an atomic force microscope during osteogenic differentiation showed a decrease in cell elasticity, which is typical of mature osteoblasts; thus the mechanical properties of AFMSCs again add to the interest in applying them in bone regenerative medicine [72] .…”

Section: In Vitro Osteogenic Differentiationmentioning

confidence: 99%

“…Moreover, some findings show that microRNAs (miRNAs) are involved in determining the fate of stem cells [70] . For example, a recent paper has shown the role of miR21 in accelerating osteogenesis of AF MSCs [71] . In that work two cellular populations were isolated from amniotic fluid: spindle-shaped (SS) and roundshaped (RS).…”

Section: In Vitro Osteogenic Differentiationmentioning

confidence: 99%

Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential

Pipino

Pandolfi

2015

WJSC

View full text Add to dashboard Cite

Human Mesenchymal Stem Cell Derived Exosomes Enhance Cell‐Free Bone Regeneration by Altering Their miRNAs Profiles

et al. 2020

View full text Add to dashboard Cite

Implantation of stem cells for tissue regeneration faces significant challenges such as immune rejection and teratoma formation. Cell-free tissue regeneration thus has a potential to avoid these problems. Stem cell derived exosomes do not cause immune rejection or generate malignant tumors. Here, exosomes that can induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) are identified and used to decorate 3D-printed titanium alloy scaffolds to achieve cell-free bone regeneration. Specifically, the exosomes secreted by hMSCs osteogenically pre-differentiated for different times are used to induce the osteogenesis of hMSCs. It is discovered that pre-differentiation for 10 and 15 days leads to the production of osteogenic exosomes. The purified exosomes are then loaded into the scaffolds. It is found that the cell-free exosome-coated scaffolds regenerate bone tissue as efficiently as hMSC-seeded exosome-free scaffolds within 12 weeks. RNA-sequencing suggests that the osteogenic exosomes induce the osteogenic differentiation by using their cargos, including upregulated osteogenic miRNAs (Hsa-miR-146a-5p, Hsa-miR-503-5p, Hsa-miR-483-3p, and Hsa-miR-129-5p) or downregulated anti-osteogenic miRNAs (Hsa-miR-32-5p, Hsa-miR-133a-3p, and Hsa-miR-204-5p), to activate the PI3K/Akt and MAPK signaling pathways. Consequently, identification of osteogenic exosomes secreted by pre-differentiated stem cells and the use of them to replace stem cells represent a novel cell-free bone regeneration strategy. 1. Introduction Bone defects can be caused by various clinical diseases such as bone infections, bone tumor, skeletal abnormalities,

show abstract

Sox2 Suppression by miR-21 Governs Human Mesenchymal Stem Cell Properties

Cited by 71 publications

References 60 publications

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential

Human Mesenchymal Stem Cell Derived Exosomes Enhance Cell‐Free Bone Regeneration by Altering Their miRNAs Profiles

Contact Info

Product

Resources

About