Engineering Extracellular Matrix‐Bound Nanovesicles Secreted by Three‐Dimensional Human Mesenchymal Stem Cells

Author:

Liu Chang1,Chen Xingchi12,Liu Yuan1ORCID,Sun Li13,Yu Zhibin24,Ren Yi3,Zeng Changchun24,Li Yan1ORCID

Affiliation:

1. Department of Chemical and Biomedical Engineering FAMU‐FSU College of Engineering Florida State University Tallahassee FL 32310 USA

2. High Performance Materials Institute FAMU‐FSU College of Engineering Florida State University Tallahassee FL 32310 USA

3. Department of Biomedical Sciences College of Medicine Florida State University Tallahassee FL 32306 USA

4. Department of Industrial and Manufacturing Engineering FAMU‐FSU College of Engineering Florida State University Tallahassee FL 32310 USA

Abstract

AbstractExtracellular matrix (ECM) in the human tissue contains vesicles, which are defined as matrix‐bound nanovesicles (MBVs). MBVs serve as one of the functional components in ECM, recapitulating part of the regulatory roles and in vivo microenvironment. In this study, extracellular vesicles from culture supernatants (SuEVs) and MBVs are isolated from the conditioned medium or ECM, respectively, of 3D human mesenchymal stem cells. Nanoparticle tracking analysis shows that MBVs are smaller than SuEVs (100–150 nm). Transmission electron microscopy captures the typical cup shape morphology for both SuEVs and MBVs. Western blot reveals that MBVs have low detection of some SuEV markers such as syntenin‐1. miRNA analysis of MBVs shows that 3D microenvironment enhances the expression of miRNAs such as miR‐19a and miR‐21. In vitro functional analysis shows that MBVs can facilitate human pluripotent stem cell‐derived forebrain organoid recovery after starvation and promote high passage fibroblast proliferation. In macrophage polarization, 2D MBVs tend to suppress the pro‐inflammatory cytokine IL‐12β, while 3D MBVs tend to enhance the anti‐inflammatory cytokine IL‐10. This study has the significance in advancing the understanding of the bio‐interface of nanovesicles with human tissue and the design of cell‐free therapy for treating neurological disorders such as ischemic stroke.

Funder

National Institutes of Health

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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