Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases

Alcaraz, Marı́a José; Compañ, Alvaro; Guillén, Marı́a Isabel

doi:10.3390/cells9010098

Cited by 62 publications

(56 citation statements)

References 155 publications

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“…Cell therapy approaches such as injection of MSCs have been recognized as a promising treatment strategy for LBP caused by IVD degeneration since MSCs can differentiate into chondrocyte-like cells and promote cell proliferation [21] and inhibit apoptosis [13]. However, several studies have provided compelling evidence indicating that the therapeutic effects of MSCs are mainly mediated by paracrine mechanisms, particularly the secretion of EVs [10,12,22,23]. Therefore, the use of hMSC-derived EVs may serve as a more appropriate alternative for treatment of IVD degeneration.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

et al. 2020

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Background Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model. Methods hMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5 × 1010 vesicles/ml concentration for 28 days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions. Results The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs. Conclusion hMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.

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Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

et al. 2020

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“…Ample evidence exists from a variety of fields that MSCderived EVs have therapeutic effects (Park et al, 2019), including musculoskeletal applications (Alcaraz et al, 2019). To ensure reproducibility of results and facilitate the exchange of data among investigators, it is essential that researchers characterize their MSCs according to the guidelines of the International Society for Cellular Therapy (plastic-adherence; lineage differentiation potential; expression of CD105, CD73 and CD90; lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19, and HLA-DR) (Dominici et al, 2006).…”

Section: Evs From Mscs: Effects On Ivd Cells and Contentmentioning

confidence: 99%

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Piazza

Dehghani

Gaborski

et al. 2020

Front. Bioeng. Biotechnol.

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Extracellular vesicles (EVs) are lipid membrane particles carrying proteins, lipids, DNA, and various types of RNA that are involved in intercellular communication. EVs derived from mesenchymal stem cells (MSCs) have been investigated extensively in many different fields due to their crucial role as regeneration drivers, but research for their use in degenerative diseases of the intervertebral disc (IVD) has only started recently. MSC-derived EVs not only promote extracellular matrix synthesis and proliferation in IVD cells, but also reduce apoptosis and inflammation, hence having multifunctional beneficial effects that seem to be mediated by specific miRNAs (such as miR-233 and miR-21) within the EVs. Aside from MSC-derived EVs, IVD-derived EVs (e.g., stemming from notochordal cells) also have important functions in IVD health and disease. This article will summarize the current knowledge on MSC-derived and IVDderived EVs and will highlight areas of future research, including the isolation and analysis of EV subpopulations or exposure of MSCs to cues that may enhance the therapeutic potential of released EVs.

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“…Cell therapy approaches such as injection of MSCs has been recognized as a promising treatment strategy for LBP caused by IVD degeneration since MSCs can differentiate into chondrocyte-like cells and promote cell proliferation [21] and inhibit apoptosis [13]. However, several studies have provided compelling evidence indicating that the therapeutic effects of MSCs are mainly mediated by paracrine mechanisms, particularly the secretion of EVs [10,12,22,23]. Therefore, the use of hMSC derived EVs may serve as a more appropriate alternative for treatment of IVD degeneration.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

Hingert

Ekström

Aldridge

et al. 2020

Preprint

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Abstract Background: Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and has been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSCs derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model. Methods: hMSCs were isolated from bone marrow aspirate and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the EVs at 5x1010 vesicles/mL concentration for 28 days and compared to control. The pellets were harvested at day 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis and cytokine secretions.Results: The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEVs treated DC pellets compared to control cultures. Further, sEVs treatment suppressed secretion of MMP-1 in the DCs. Conclusion: hMSC derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.

show abstract

Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases

Cited by 62 publications

References 155 publications

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

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