Post-production modifications of murine mesenchymal stem cell (mMSC) derived extracellular vesicles (EVs) and impact on their cellular interaction

Saux, Sarah Le; Aarrass, Hanna; Lai-Kee-Him, Joséphine; Bron, Patrick; Armengaud, Jean; Miotello, Guylaine; Bertrand‐Michel, Justine; Dubois, Emeric; George, Simon C.; Faklaris, Orestis; Devoisselle, Jean-Marie; Legrand, Philippe; Chopineau, Joël; Morille, Marie

doi:10.1016/j.biomaterials.2019.119675

Cited by 71 publications

(83 citation statements)

References 83 publications

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“…Rapid and direct interactions of molecules with extravesicular microenvironment are crucial for EVs. [ 13,38,39 ] Smaller‐sized vesicles are more favorable for L‐EVs to deposit onto collagen and facilitate mineralization. [ 40,41 ] We performed TEM scanning of EVs without negative staining to avoid dye impurities according to previously published protocol.…”

Section: Resultsmentioning

confidence: 99%

Autologous Versatile Vesicles‐Incorporated Biomimetic Extracellular Matrix Induces Biomineralization

Wei

Shi

Zhang

et al. 2020

Adv Funct Materials

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Restoring extracellular matrix (ECM) with supportive and osteoinductive abilities is of great significance for bone tissue regeneration. Current approaches involving cell-based scaffolds or nanoparticle-modified biomimic-ECM have been met with additional biosafety concerns. Herein, the natural biomineralization process is first analyzed and is found that mesenchymal stem cells-derived extracellular vesicles (EVs) from early and late stages of osteoinduction play different roles during the mineralization process. The functional EVs hierarchically with blood-derived autohydrogel (AH) are then incorporated to form an osteoinductive biomimetic extracellular matrix (BECM). The alkaline phosphatase-rich EVs are released from the outer layers to induce osteoblast differentiation during early stages. Thereafter, as the degradation of AH occurred, calcium/phosphorus (Ca/P)rich EVs are liberated to promote the nucleation of extracellular mineral crystals. Additionally, BECM contains considerable collagen fibrils that provide additional nucleation sites for crystallites deposition, thus reaching self-mineralization in situ. In conclusion, this research provides a promising, versatile mineralization-instructive platform to tackle the challenges faced in bone-tissue engineering. Scheme 1. Illustration of the BECM induced osteogenesis and biomineralization. In the early stage of mineralization, BECM secreted ALP-rich E-EVs. The E-EVs moved to intracellular mitochondria and provided ALP for phosphate metabolism, contributing to the formation of Ca/P-rich vesicles. Later, with the degradation of BECM, Ca/P-rich L-EVs were released gradually. The L-EVs aligned to extracellular collagen and promoted the nucleation of extracellular mineral crystals. Besides, L-EVs inside BECM aggregate around the internally collagen fibrils and initiated in situ mineralization. Finally, with the complete degradation of BECM, the internal mineralized components were released to the extracellular matrix, promoting the deposition formation together to realize an ideal self-mineralization process for bone tissue regeneration.www.afm-journal.de www.advancedsciencenews.com (3 of 15)

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Section: Resultsmentioning

confidence: 99%

Autologous Versatile Vesicles‐Incorporated Biomimetic Extracellular Matrix Induces Biomineralization

Wei

Shi

Zhang

et al. 2020

Adv Funct Materials

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“…EVs can also be loaded with drugs by cell transfection and genetic expression of a candidate gene, or by drug encapsulation after their isolation [( Mao et al, 2019 ; He et al, 2020 ; Ou et al, 2020 ); for review, see Crivelli et al (2017) ]. MSC-EVs were extensively characterized as drug delivery platform and shown to have greater internalization capabilities than commercial liposomes ( Le Saux et al, 2020 ). The interest of using MSC-EVs loaded with doxorubicin by electroporation to target murine breast cancer cells or osteosarcoma cells has been demonstrated ( Gomari et al, 2019 ; Wei et al, 2019 ).…”

Section: Potential Therapeutic Use Of Mesenchymal Stem Cell-derived Ementioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

Maumus

Rozier

Boulestreau

et al. 2020

Front. Bioeng. Biotechnol.

105

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Extracellular vesicles (EVs), including exosomes and microvesicles, derived from mesenchymal stem/stromal cells (MSCs) exert similar effects as their parental cells, and are of interest for various therapeutic applications. EVs can act through uptake by the target cells followed by release of their cargo inside the cytoplasm, or through interaction of membrane-bound ligands with receptors expressed on target cells to stimulate downstream intracellular pathways. EV-based therapeutics may be directly used as substitutes of intact cells or after modification for targeted drug delivery. However, for the development of EV-based therapeutics, several production, isolation, and characterization requirements have to be met and the quality of the final product has to be tested before its clinical implementation. In this review, we discuss the challenges associated with the development of EV-based therapeutics and the regulatory specifications for their successful clinical translation.

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“…This implies the choice between storage in liquid nitrogen (or better, in the gas phase above liquid nitrogen, at about −180 • C) or the employment of a mechanical refrigeration freezer able to reach these temperatures, each with their advantages and drawbacks [103]. Differently, an emerging number of studies demonstrated that frozen EVs are stable if stored at −80 • C for long periods [107], implying a lower cost for the equipment and its management. Moreover, in contrast to the cell products, EVs can be lyophilized or freeze-dried, increasing the EVs' shelf life and reducing the storage demands and the costs associated with a simpler cold chain.…”

Section: Open Industrial Challengesmentioning

confidence: 99%

Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective

Arrigoni

D’Arrigo

Rossella³

et al. 2020

Cells

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The prevalence of arthritic diseases is increasing in developed countries, but effective treatments are currently lacking. The injection of mesenchymal stem cells (MSCs) represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA). However, the majority of clinical approaches based on MSCs are used within an autologous paradigm, with important limitations. For this reason, allogeneic MSCs isolated from cord blood (cbMSCs) and Wharton’s jelly (wjMSCs) gained increasing interest, demonstrating promising results in this field. Moreover, recent evidences shows that MSCs beneficial effects can be related to their secretome rather than to the presence of cells themselves. Among the trophic factors secreted by MSCs, extracellular vesicles (EVs) are emerging as a promising candidate for the treatment of arthritic joints. In the present review, the application of umbilical cord MSCs and their secretome as innovative therapeutic approaches in the treatment of arthritic joints will be examined. With the prospective of routine clinical applications, umbilical cord MSCs and EVs will be discussed also within an industrial and regulatory perspective.

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Post-production modifications of murine mesenchymal stem cell (mMSC) derived extracellular vesicles (EVs) and impact on their cellular interaction

Cited by 71 publications

References 83 publications

Autologous Versatile Vesicles‐Incorporated Biomimetic Extracellular Matrix Induces Biomineralization

Autologous Versatile Vesicles‐Incorporated Biomimetic Extracellular Matrix Induces Biomineralization

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective

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