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
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.
引用
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页数:21
相关论文
共 268 条
[1]
Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes [J].
Alvarez-Erviti, Lydia ;
Seow, Yiqi ;
Yin, HaiFang ;
Betts, Corinne ;
Lakhal, Samira ;
Wood, Matthew J. A. .
NATURE BIOTECHNOLOGY, 2011, 29 (04) :341-U179
[3]
Amado LC, 2005, P NATL ACAD SCI USA, V102, P11474, DOI 10.1073/pnas.0504388102
[4]
Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling [J].
Anderson, Johnathon D. ;
Johansson, Henrik J. ;
Graham, Calvin S. ;
Vesterlund, Mattias ;
Pham, Missy T. ;
Bramlett, Charles S. ;
Montgomery, Elizabeth N. ;
Mellema, Matt S. ;
Bardini, Renee L. ;
Contreras, Zelenia ;
Hoon, Madeline ;
Bauer, Gerhard ;
Fink, Kyle D. ;
Fury, Brian ;
Hendrix, Kyle J. ;
Chedin, Frederic ;
El-Andaloussi, Samir ;
Hwang, Billie ;
Mulligan, Michael S. ;
Lehtio, Janne ;
Nolta, Jan A. .
STEM CELLS, 2016, 34 (03) :601-613
[5]
SYNERGISTIC EFFECT OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR ON ANGIOGENESIS IN-VIVO [J].
ASAHARA, T ;
BAUTERS, C ;
ZHENG, LP ;
TAKESHITA, S ;
BUNTING, S ;
FERRARA, N ;
SYMES, JF ;
ISNER, JM .
CIRCULATION, 1995, 92 (09) :365-371
[6]
A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure [J].
Atkin-Smith, Georgia K. ;
Tixeira, Rochelle ;
Paone, Stephanie ;
Mathivanan, Suresh ;
Collins, Christine ;
Liem, Michael ;
Goodall, Katharine J. ;
Ravichandran, Kodi S. ;
Hulett, Mark D. ;
Poon, Ivan K. H. .
NATURE COMMUNICATIONS, 2015, 6
[7]
Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species [J].
Baglio, Serena Rubina ;
Rooijers, Koos ;
Koppers-Lalic, Danijela ;
Verweij, Frederik J. ;
Lanzon, M. Perez ;
Zini, Nicoletta ;
Naaijkens, Benno ;
Perut, Francesca ;
Niessen, Hans W. M. ;
Baldini, Nicola ;
Pegtel, D. Michiel .
STEM CELL RESEARCH & THERAPY, 2015, 6
[8]
Dissection of the Cord Blood Stromal Component Reveals Predictive Parameters for Culture Outcome [J].
Barilani, Mario ;
Lavazza, Cristiana ;
Vigano, Mariele ;
Montemurro, Tiziana ;
Boldrin, Valentina ;
Parazzi, Valentina ;
Montelatici, Elisa ;
Crosti, Mariacristina ;
Moro, Monica ;
Giordano, Rosaria ;
Lazzari, Lorenza .
STEM CELLS AND DEVELOPMENT, 2015, 24 (01) :104-114
[9]
Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties [J].
Bartosh, Thomas J. ;
Ylostalo, Joni H. ;
Mohammadipoor, Arezoo ;
Bazhanov, Nikolay ;
Coble, Katie ;
Claypool, Kent ;
Lee, Ryang Hwa ;
Choi, Hosoon ;
Prockop, Darwin J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (31) :13724-13729
[10]
Becquart P, 2012, TISSUE ENG PT A, V18, P2084, DOI [10.1089/ten.TEA.2011.0690, 10.1089/ten.tea.2011.0690]