Abstract
Extracellular vesicles (EVs) are mediators of intercellular communication by transferring functional biomolecules from their originating cells to recipient cells. This intrinsic ability has gained EVs increased scientific interest in their use as a direct therapeutic in the field of regenerative medicine or as vehicles for drug delivery. EVs derived from stem cells or progenitor cells can act as paracrine mediators to promote repair and regeneration of damaged tissues. Despite substantial research efforts into EVs for various applications, their use remains limited by the lack of highly efficient and scalable production methods. Here, we present the biofabrication of cell-derived nanovesicles (NVs) as a scalable, efficient, and cost-effective production alternative to EVs. We demonstrate that NVs have a comparable size and morphology as EVs, but lack standard EV (surface) markers. Additionally, in vitro uptake experiments show that human fetal cardiac fibroblast, endothelial cells, and cardiomyocyte progenitor cells internalize NVs. We observed that cardiac progenitor cell-derived NVs and EVs are capable of activating mitogen-activated protein kinase 1/2 (MAPK1/2)-extracellular signal-regulated kinase, and that both NVs and EVs derived from A431 and HEK293 cells can functionally deliver Cre-recombinase mRNA or protein to other cells. These observations indicate that NVs may have similar functional properties as EVs. Therefore, NVs have the potential to be applied for therapeutic delivery and regenerative medicine purposes.
Highlights
Extracellular vesicles (EVs) are cell-derived nanoparticles consisting of a lipid bilayer encapsulating cytosolic content from their cell of origin
We investigate the biofabrication of NVs as an alternative production production method to make aimed to investigate biofabrication of NVs asself-assembly an alternativeofproduction method to make biofabrication is the based on the spontaneous phospholipids, which are EV
The study of Park et al (2019) demonstrated that mesenchymal stromal cell-derived nanovesicles are enriched with CD81, flotillin-1, and β-actin, while we only found cardiac progenitor cell (CPC)-EVs to be enriched with CD81 [33]
Summary
Extracellular vesicles (EVs) are cell-derived nanoparticles consisting of a lipid bilayer encapsulating cytosolic content from their cell of origin. EVs can exchange information between cells by delivering biomolecules, e.g., proteins, nucleic acids, or lipids, from their parent cells to target cells [1]. EVs0 endogenous origin, low immunogenicity, intrinsic targeting abilities, and biocompatibility are potential advantages features compared to conventional drug delivery systems such as liposomes, polymers, and gold particles [2,3,4]. Human fetal cardiac progenitor cell (CPC)-derived EVs stimulate pro-angiogenic effects and improve cardiac function upon injury [12,13]. CPC-EVs are an attractive therapeutic candidate to stimulate cardiac repair and regeneration, since the heart has a very poor endogenous regenerative capacity [14,15,16,17,18]
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