Deterministic paracrine repair of injured myocardium using microfluidic-based cocooning of heart explant-derived cells

Pushpinder Kanda; Ainara Benavente-Babace; Sandrine Parent; Michie Connor; Nicholas Soucy; Alexander Steeves; Aizhu Lu; Nicholas David Cober; David Courtman; Fabio Variola; Emilio I Alarcon; Wenbin Liang; Duncan J Stewart; Michel Godin; Darryl R Davis

doi:10.1016/j.biomaterials.2020.120010

Deterministic paracrine repair of injured myocardium using microfluidic-based cocooning of heart explant-derived cells

Biomaterials. 2020 Jul:247:120010. doi: 10.1016/j.biomaterials.2020.120010. Epub 2020 Apr 2.

Authors

Affiliations

¹ University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, K1Y4W7, Canada.
² Department of Physics, University of Ottawa, K1N6N5, Canada.
³ Ottawa-Carleton Institute for Biomedical Engineering, Ottawa, K1N6N5, Canada.
⁴ Department of Mechanical Engineering, University of Ottawa, K1N6N5, Canada.
⁵ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H8M5, Canada.
⁶ Ottawa Hospital Research Institute, Division of Regenerative Medicine, Department of Medicine, University of Ottawa, Ottawa, K1H8L6, Canada.
⁷ University of Ottawa Heart Institute, Division of Cardiac Surgery, Department of Medicine, University of Ottawa, Ottawa, K1Y4W7, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, K1H8M5, Canada.
⁸ University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, K1Y4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H8M5, Canada.
⁹ Ottawa Hospital Research Institute, Division of Regenerative Medicine, Department of Medicine, University of Ottawa, Ottawa, K1H8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H8M5, Canada.
¹⁰ Department of Physics, University of Ottawa, K1N6N5, Canada; Ottawa-Carleton Institute for Biomedical Engineering, Ottawa, K1N6N5, Canada; Department of Mechanical Engineering, University of Ottawa, K1N6N5, Canada.
¹¹ University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, K1Y4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H8M5, Canada. Electronic address: ddavis@ottawaheart.ca.

PMID: 32259654
DOI: 10.1016/j.biomaterials.2020.120010

Abstract

While encapsulation of cells within protective nanoporous gel cocoons increases cell retention and pro-survival integrin signaling, the influence of cocoon size and intra-capsular cell-cell interactions on therapeutic repair are unknown. Here, we employ a microfluidic platform to dissect the impact of cocoon size and intracapsular cell number on the regenerative potential of transplanted heart explant-derived cells. Deterministic increases in cocoon size boosted the proportion of multicellular aggregates within cocoons, reduced vascular clearance of transplanted cells and enhanced stimulation of endogenous repair. The latter being attributable to cell-cell stimulation of cytokine and extracellular vesicle production while also broadening of the miRNA cargo within extracellular vesicles. Thus, by tuning cocoon size and cell occupancy, the paracrine signature and retention of transplanted cells can be enhanced to promote paracrine stimulation of endogenous tissue repair.

Keywords: Extracellular vesicle; Heart failure; Microfluidic device; Myocardial infarction; Nanoporous gel; Stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Extracellular Vesicles*
Heart
Humans
Microfluidics
Myocardial Infarction*
Myocardium
Paracrine Communication

Abstract

Publication types

MeSH terms

Grants and funding