Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis

Zhang, Bocheng; Tian, Xiaoyuan; Qu, Zhenan; Hao, Jun; Zhang, Weiguo

doi:10.3390/membranes12020225

Cited by 35 publications

(44 citation statements)

References 36 publications

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“…Thus, in vivo assays have shown that an injectable silk-fibroin hydrogel, containing articular chondrocytes and MSC-derived EV in hypoxia promoted cartilage regeneration[ 120 ]. Several miRNA were involved in this process, including miR-18a-3p, miR-181c-5p, miR-205-5p, miR-337-5p, and miR-376a-5p[ 120 , 121 ].…”

Section: Therapeutic Potential Of Ev Derived From Msc Preconditioned ...mentioning

confidence: 99%

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

Pulido-Escribano¹,

Torrecillas-Baena²,

Camacho-Cardeñosa³

et al. 2022

WJSC

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The use of mesenchymal stem-cells (MSC) in cell therapy has received considerable attention because of their properties. These properties include high expansion and differentiation in vitro , low immunogenicity, and modulation of biological processes, such as inflammation, angiogenesis and hematopoiesis. Curiously, the regenerative effect of MSC is partly due to their paracrine activity. This has prompted numerous studies, to investigate the therapeutic potential of their secretome in general, and specifically their extracellular vesicles (EV). The latter contain proteins, lipids, nucleic acids, and other metabolites, which can cause physiological changes when released into recipient cells. Interestingly, contents of EV can be modulated by preconditioning MSC under different culture conditions. Among them, exposure to hypoxia stands out; these cells respond by activating hypoxia-inducible factor (HIF) at low O 2 concentrations. HIF has direct and indirect pleiotropic effects, modulating expression of hundreds of genes involved in processes such as inflammation, migration, proliferation, differentiation, angiogenesis, metabolism, and cell apoptosis. Expression of these genes is reflected in the contents of secreted EV. Interestingly, numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia. In this review, we show the implications of hypoxia responses in relation to tissue regeneration. In addition, hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV, with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

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Section: Therapeutic Potential Of Ev Derived From Msc Preconditioned ...mentioning

confidence: 99%

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

Pulido-Escribano¹,

Torrecillas-Baena²,

Camacho-Cardeñosa³

et al. 2022

WJSC

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“…Next, we compared our results with other works that evaluated the miRNA content of N- and H-EVs [ 59 , 60 , 61 ]. It is noteworthy that the analyzed studies used different cells to produce the EVs and had differences in the methodologies and parameters of analysis.…”

Section: Resultsmentioning

confidence: 99%

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

Robert

Marcon

Angulski

et al. 2022

IJMS

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Endothelial-like cells may be obtained from CD133+ mononuclear cells isolated from human umbilical cord blood (hUCB) and expanded using endothelial-inducing medium (E-CD133 cells). Their use in regenerative medicine has been explored by the potential not only to form vessels but also by the secretion of bioactive elements. Extracellular vesicles (EVs) are prominent messengers of this paracrine activity, transporting bioactive molecules that may guide cellular response under different conditions. Using RNA-Seq, we characterized the miRNA content of EVs derived from E-CD133 cells cultivated under normoxia (N-EVs) and hypoxia (H-EVs) and observed that changing the O2 status led to variations in the selective loading of miRNAs in the EVs. In silico analysis showed that among the targets of differentially loaded miRNAs, there are transcripts involved in pathways related to cell growth and survival, such as FoxO and HIF-1 pathways. The data obtained reinforce the pro-regenerative potential of EVs obtained from E-CD133 cells and shows that fine tuning of their properties may be regulated by culture conditions.

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Section: Cell-based Therapies For Osteoarthritismentioning

confidence: 99%

“…Culture-expanded MSCs may exert a therapeutic effect through immune modulation and via trophic actions on local joint cells through secreted factors without directly participating in new cartilage formation ( Mak et al, 2016 ; Zhang et al, 2022 ). Consequently, non-cellular biologically-based strategies harnessing the MSC secretome have been explored for cartilage and bone repair ( Kalluri and LeBleu, 2020 ; To et al, 2020 ; Zhang et al, 2022 ). MSC-derived extracellular vesicles (MSC-EVs) are MSC-produced nanovesicles ranging from 10 nm to several μm in diameter that contain components such as messenger RNA, microRNA, lipids, and bioactive proteins that produce regenerative paracrine effects within damaged tissue ( To et al, 2020 ).…”

Section: Cell-based Therapies For Osteoarthritismentioning

confidence: 99%

The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration

Campbell

Dilworth

Allan

et al. 2022

Front. Bioeng. Biotechnol.

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Cartilage injury and degeneration are hallmarks of osteoarthritis (OA), the most common joint disease. OA is a major contributor to pain, loss of function, and reduced quality of life. Over the last decade, considerable research efforts have focused on cell-based therapies, including several stem cell-derived approaches to reverse the cartilage alterations associated with OA. Although several tissue sources for deriving cell-based therapies have been identified, none of the resident stem cell populations have adequately fulfilled the promise of curing OA. Indeed, many cell products do not contain true stem cells. As well, issues with aggressive marketing efforts, combined with a lack of evidence regarding efficacy, lead the several national regulatory bodies to discontinue the use of stem cell therapy for OA until more robust evidence becomes available. A review of the evidence is timely to address the status of cell-based cartilage regeneration. The promise of stem cell therapy is not new and has been used successfully to treat non-arthritic diseases, such as hematopoietic and muscle disorders. These fields of regenerative therapy have the advantage of a considerable foundation of knowledge in the area of stem cell repair mechanisms, the role of the stem cell niche, and niche-supporting cells. This foundation is lacking in the field of cartilage repair. So, where should we look for the ideal stem cell to regenerate cartilage? It has recently been discovered that cartilage itself may contain a population of SC-like progenitors. Other potential tissues include stem cell-rich dental pulp and the adolescent growth plate, the latter of which contains chondrocyte progenitors essential for producing the cartilage scaffold needed for bone growth. In this article, we review the progress on stem cell therapies for arthritic disorders, focusing on the various stem cell populations previously used for cartilage regeneration, successful cases of stem cell therapies in muscle and hemopoietic disorders, some of the reasons why these other fields have been successful (i.e., “lessons learned” to be applied to OA stem cell therapy), and finally, novel potential sources of stem cells for regenerating damaged cartilage in vivo.

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Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis

Cited by 35 publications

References 36 publications

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration

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