Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

Ragni, Enrico; Orfei, Carlotta Perucca; Luca, Paola De; Colombini, Alessandra; Viganò, Marco; Girolamo, Laura de

doi:10.3390/ijms21051582

Cited by 53 publications

(58 citation statements)

References 110 publications

(112 reference statements)

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“…Under this final analysis, miR-101-3p emerged as the best candidate (geomean of 1.32), tightly followed by miR-22-5p (1.41). Conversely, miR-423-5p (8) and U6 snRNA (9) clearly ranked last, making their choice unfavorable.…”

Section: Rgs Stability Analysismentioning

confidence: 99%

“…As an example, in the orthopedic field, which is one of the most actively studied areas in regenerative medicine, miRNA-enriched MSC-EVs were shown to promote cartilage regeneration [5,6] by modulating ECM production. Similarly, in adipose-derived MSCs (ASCs), inflammatory priming of cells was able to modulate the EVs incorporation of miRNAs involved in both cartilage homeostasis and macrophage M2-polarization [8,9]. Thus, there is a growing interest in both the discovery and characterization of new MSC-EVs for their future use as natural or engineered delivery platforms in regenerative approaches.…”

Section: Introductionmentioning

confidence: 99%

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miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

et al. 2020

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Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and ΔCt method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields.

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Section: Rgs Stability Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

et al. 2020

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“…On the contrary, miR-24-3p upregulation could promote intervertebral disc degeneration through IGFBP5 and the ERK signaling pathway [25]. According to the report by Ragni et al [17] who showed a strong capacity for adipose-derived MSCs (ASCs) to reduce matrix degradation activities, we thus inferred that miR-24-3p suppressed OA progression might via inhibiting apoptosis, in ammation and ECM degradation.…”

Section: Discussionmentioning

confidence: 80%

“…Similarly, Shen et al [16] demonstrated that miR-24-3p may ameliorate in ammatory response and cellular apoptosis in hepatic I/R process, which might be a potential therapeutic target for preventing liver I/R development and progression. Interestingly, a recent study by Ragni et al [17] who pointed that miR-24-3p was involved in adipose-derived mesenchymal stem cells (ASCs) regulating cell homeostasis and regenerative pathways in an OA-resembling environment. However, the involvement and underlying mechanism of miR-24-3p in chondrocyte injury associated with the pathogenesis of OA remains unknown.…”

Section: Introductionmentioning

confidence: 99%

MiR-24-3p Attenuates IL-1β-Induced Chondrocyte Injury Associated With Osteoarthritis by Targeting BCL2L12

Xu¹,

Qian

Ren

2020

Preprint

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Background: Osteoarthritis (OA) is a chronic and degenerative joint disease prevalent in the elderly. MiR-24-3p has been reported to be involved in an OA-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods: The expression of miR-24-3p was determined in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001 using reverse transcription quantitative PCR analysis. Cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and BCL2L12 was confirmed by luciferase reporter assay.Results: We first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury.Conclusions: In conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.

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“…Chang et al demonstrated that ADSCs suppress osteoclastogenesis and bone erosion in collagen-induced arthritis [63]. In addition, secreted factors and EV-miRNAs orchestrate the healing capacity of ADSCs in treating knee osteoarthritis [64]. Cowan et al demonstrated that the effects of ADSC transplantation repairing skull defect was great, and there were no needs for any treatment for ADSCs in vitro or adding any simulating factors.…”

Section: Adsc Transplantation In Bone Joint and Muscle Systemmentioning

confidence: 99%

Recent Advances of Adipose-Derived Stem Cell-Based Therapies

Qi¹

2020

Molecular Biology &Amp; Nanomedicine

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Adipose-derived stem cells (ADSCs), which were initially isolated from the aspirate of human fat by Zuk et al, are considered as an attractive cell source of mesenchymal stem cells (MSCs) for cell-based therapies. Due to their easily accessible, broader sources of multipotent cells and stronger ability for amplification in vitro, ADSCs have attracted considerable attention and curiosity from both scientific and clinical communities for their potential mechanisms in future stem cell treatments. Furthermore, their promising therapeutic characteristics were the unique ability of immunosuppression, secretory function and the potential for multi-directional differentiation. With more research efforts made to understand their effects on both scientific and clinical fields, ADSCs possess great potential as a future therapeutic strategy in treatment for widely various diseases. Therefore, this review intends to lay stress on the clinical application of ADSCs and their advancement in clinical trials across a variety of medical disciplines. Due to their advantages in various fields, ADSCs have a strong potential for application in future stem cell treatments and are beneficial for allogenic transplantation treatments. ADSCs may be considered as an alternative in cell transplantation and tissue engineering clinical treatments.

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Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

Cited by 53 publications

References 110 publications

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

MiR-24-3p Attenuates IL-1β-Induced Chondrocyte Injury Associated With Osteoarthritis by Targeting BCL2L12

Recent Advances of Adipose-Derived Stem Cell-Based Therapies

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