Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb

Han, Chaoshan; Zhou, Jin; Liu, Bin; Liang, Chun; Pan, Xiangbin; Zhang, Yu; Wang, Yanli; Shao, Liqun; Zhu, Bao Ting; Wang, Juanjuan; Yin, Qian; Yu, Xiang; Li, Yangxin

doi:10.1016/j.msec.2019.01.122

Cited by 101 publications

(81 citation statements)

References 61 publications

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“…[ 229 ] Interestingly, delivery of miR‐675, previously shown to promote muscle regeneration, [ 230 ] by EVs from miR‐675 overexpressing MSCs encapsulated in a silk fibroin hydrogel prevented ischemia‐induced vascular dysfunction in muscles by inhibiting the TGF‐β1/p21 pathway. [ 231 ]…”

Section: Biomaterials Functionalized With Msc Secretomementioning

confidence: 99%

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Brennan

Layrolle

Mooney

2020

Adv Funct Materials

220

196

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The therapeutic benefits of mesenchymal stromal cell (MSC) transplantation are attributed to their secreted factors, including extracellular vesicles (EVs) and soluble factors. The potential of employing the MSC secretome as an alternative acellular approach to cell therapy is being investigated in various tissue injury indications, but EVs administered via bolus injections are rapidly sequestered and cleared. However, biomaterials offer delivery platforms to enhance EV retention rates and healing efficacy. This review highlights the mechanisms underpinning the therapeutic effects of MSC‐EVs and soluble factors as effectors of immunomodulation and tissue regeneration, conferred primarily via their nucleic acid and protein contents. Discussed is how manipulating the cell culture microenvironment or genetic modification of MSCs can further augment the potency of their secretions. The most recent advances in the development of EV‐functionalized biomaterials that mediate enhanced angiogenesis and cell survival, while attenuating inflammation and fibrosis, are presented. Finally, some technical challenges to be considered for the clinical translation of biomaterials carrying MSC‐secreted bioactive cargo are discussed.

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Section: Biomaterials Functionalized With Msc Secretomementioning

confidence: 99%

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Brennan

Layrolle

Mooney

2020

Adv Funct Materials

220

196

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“…3D scaffolds could be further used as working platforms for the exosomes while attempting to control the release of exosomes in the tissue repaired area [63][64] . Hydrogel has been widely used as 3D scaffold due to their unique features, such as high water content, biocompatibility, swelling behavior, and modulated 3D networks, in many restorative areas, such as cardiac repair [65] , vascular disease [66] , wound healing [67] . Recently, Zhang et al reported that chitosan hydrogel could notably increase the stability of proteins and miRNAs in exosomes [68] .…”

Section: D Biomaterials and Exosome Retentionmentioning

confidence: 99%

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

et al. 2020

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Articular cartilage injury is a common clinical problem, which can lead to joint dysfunction, significant pain, and secondary osteoarthritis (OA) in which major surgical procedures are mandatory for treatment. Exosomes, as endosome-derived membrane-bound vesicles, participating in intercellular communications in both physiological and pathophysiological conditions, have been attached great importance in many fields. Recently, the significance of exosomes in the development of OA has been gradually concerned, while the therapeutic value of exosomes in cartilage repair and OA treatment has also been gradually revealed. The functional difference of different types and derivations of exosomes are determined by their specific contents. Herein, we provide comprehensive understanding on exosome and OA, including how exosomes participating in OA, the therapeutic value of exosomes for cartilage injury/OA, and related bioengineering strategies for future therapeutic design.

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“…Transfection or transduction, though still an indirect method of cargo loading compared to electroporation or other active methods for exogenous cargo loading, offers more control than preconditioning. Umbilical cord MSCs were transfected with miR-675 mimic, leading to the secretion of EVs that showed increased expression of miR-675 [73]. When tested in a murine model for aging-induced vascular dysfunction, the miR-675-enriched EVs, delivered in silk fibroin hydrogels, successfully promoted blood perfusion in ischemic hindlimbs and reduced the expression of proinflammatory molecules.…”

Section: Nucleic Acidsmentioning

confidence: 99%

“…Small molecules [64,67,68] miRNA [70,[73][74][75] Protein [79] Freeze/thaw cycle EV and cargo molecules are incubated together at room temperature and then rapidly frozen at <−80 • C and thawed at room temperature. The freezing disrupts the membrane, which allows the cargo molecules to diffuse into the EVs while in a semi-frozen state during the thawing process.…”

Section: Passivementioning

confidence: 99%

Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine

2019

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Long thought of to be vesicles that primarily recycled waste biomolecules from cells, extracellular vesicles (EVs) have now emerged as a new class of nanotherapeutics for regenerative medicine. Recent studies have proven their potential as mediators of cell proliferation, immunomodulation, extracellular matrix organization and angiogenesis, and are currently being used as treatments for a variety of diseases and injuries. They are now being used in combination with a variety of more traditional biomaterials and tissue engineering strategies to stimulate tissue repair and wound healing. However, the clinical translation of EVs has been greatly slowed due to difficulties in EV isolation and purification, as well as their limited yields and functional heterogeneity. Thus, a field of EV engineering has emerged in order to augment the natural properties of EVs and to recapitulate their function in semi-synthetic and synthetic EVs. Here, we have reviewed current technologies and techniques in this growing field of EV engineering while highlighting possible future applications for regenerative medicine.

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Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb

Cited by 101 publications

References 61 publications

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine

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