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

被引：336

作者：

Brennan, Meadhbh A. ^{[1
,2
]}

Layrolle, Pierre ^{[2
]}

Mooney, David J. ^{[1
,3
]}

机构：

[1] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA

[2] Univ Nantes, Fac Med, Lab Bone Sarcomas & Remodeling Calcified Tissues, INSERM,PhyOS,UMR 1238, F-44035 Nantes, France

[3] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA

来源：

ADVANCED FUNCTIONAL MATERIALS | 2020年 / 30卷 / 37期

基金：

欧盟地平线“2020”;

关键词：

exosomes; extracellular vesicles; functionalized biomaterials; hydrogels; mesenchymal stromal cells; tissue regeneration; MESENCHYMAL STEM-CELLS; ENDOTHELIAL GROWTH-FACTOR; HYPOXIC CONDITIONED MEDIUM; MARROW STROMAL CELLS; HUMAN ADIPOSE-TISSUE; BONE REGENERATION; MYOCARDIAL-INFARCTION; ENGINEERED CONSTRUCTS; THERAPEUTIC-EFFICACY; PROMOTE ANGIOGENESIS;

D O I：

10.1002/adfm.201909125

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

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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