Pro-Chondrogenic Effect of miR-221 and Slug Depletion in Human MSCs

Lolli, Andrea; Lambertini, Elisabetta; Penolazzi, Letizia; Angelozzi, Marco; Morganti, Claudia; Franceschetti, Tiziana; Pelucchi, Stefano; Gambari, Roberto; Piva, Roberta

doi:10.1007/s12015-014-9532-1

Cited by 36 publications

(56 citation statements)

References 49 publications

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“…[159] This study was validated here both in pellet culture and additionally in vivo. [161] This study was validated here both in 3D pellet culture and additionally in vivo. [112] Lipofectamine RNAiMAXmiR-221 inhibitor was used to transfect monolayer BM-MSCs and showed higher than 95% miR-221 knockdown before resuspension in alginate.…”

Section: Cartilage Repairmentioning

confidence: 71%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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Section: Cartilage Repairmentioning

confidence: 71%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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“…Total cell extracts were prepared from cells exposed to normoxia or hypoxia condition as previously reported [25]. 20 μg of each sample were electrophoresed through a 4-15% SDS-polyacrylamide gradient gel.…”

Section: Western Blot Analysismentioning

confidence: 99%

Hypoxia Preconditioning of Human MSCs: a Direct Evidence of HIF-1α and Collagen Type XV Correlation

Lambertini

Penolazzi

Angelozzi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Mesenchymal stromal cells (MSCs) hold considerable promise in bone tissue engineering, but their poor survival and potency when in vivo implanted limits their therapeutic potential. For this reason, the study on culture conditions and cellular signals that can influence the potential therapeutic outcomes of MSCs have received considerable attention in recent years. Cell maintenance under hypoxic conditions, in particular for a short period, is beneficial for MSCs, as low O₂ tension is similar to that present in the physiologic niche, however the precise mechanism through which hypoxia preconditioning affects these cells remains unclear. Methods: In order to explore what happens during the first 48 h of hypoxia preconditioning in human MSCs (hMSCs) from bone marrow, the cells were exposed to 1.5% O₂ tension in the X3 Hypoxia Hood and Culture Combo – Xvivo System device. The expression modulation of critical genes which could be good markers of increased osteopotency has been investigated by Western blot, immunufluorescence and ELISA. Luciferase reporter assay and Chromatin immunoprecipitation was used to investigate the regulation of the expression of Collagen type XV (ColXV) gene. Results: We identified ColXV as a new low O₂ tension sensitive gene, and provided a novel mechanistic evidence that directly HIF-1α (hypoxia-inducible factor-1 alpha) mediates ColXV expression in response to hypoxia, since it was found specifically in vivo recruited at ColXV promoter, in hypoxia-preconditioned hMSCs. This finding, together the evidence that also Runx2, VEGF and FGF-2 expression increased in hypoxia preconditioned hMSCs, is consistent with the possibility that increased ColXV expression in response to hypoxia is mediated by an early network that supports the osteogenic potential of the cells. Conclusion: These results add useful information to understand the role of a still little investigated collagen such as ColXV, and identify ColXV as a marker of successful hypoxia preconditioning. As a whole, our data give further evidence that hypoxia preconditioned hMSCs have greater osteopotency than normal hMSCs, and that the effects of hypoxic regulation of hMSCs activities should be considered before they are clinically applied.

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“…SOX9 and RUNX2) and adhesion molecules. Among the EMT-regulators, TWIST1 and SLUG/SNAIL2 were validated as targets for enhancing the chondrogenic potential [59][60][61]. We previously showed that treating hMSCs from different sources with a siRNA against SLUG induced chondrogenesis and production of cartilage ECM in a 3D-microenvironment.…”

Section: Silencing Of Transcription Factorsmentioning

confidence: 99%

“…Enhanced hMSCs-mediated in vivo cartilage repair [32,60] miR-222 Enhanced chondrogenesis and osteogenesis of hMSCs in vitro. Improved angiogenesis and bone union and healing in vivo [102] circRNA-CER Increased expression of collagen II and aggrecan in human OA chondrocytes.…”

Section: Silencing Of Non-coding Rnasmentioning

confidence: 99%

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

Lolli

Penolazzi

Narcisi

et al. 2017

Cell. Mol. Life Sci.

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The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury. Different types of molecules including transcription factors, transcriptional co-regulators, secreted proteins, and microRNAs have recently been identified as negative modulators of chondroprogenitor differentiation and chondrocyte function. We review the current knowledge about these molecules as potential targets for gene knockdown strategies using RNA interference (RNAi) tools that allow the specific suppression of gene function. The critical issues regarding the optimization of the gene silencing approach as well as the delivery strategies are discussed. We anticipate that further development of these techniques will lead to the generation of implantable hMSCs with enhanced potential to regenerate articular cartilage damaged by injury, disease, or aging.

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Pro-Chondrogenic Effect of miR-221 and Slug Depletion in Human MSCs

Cited by 36 publications

References 49 publications

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Hypoxia Preconditioning of Human MSCs: a Direct Evidence of HIF-1α and Collagen Type XV Correlation

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

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