Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth.

Qi Hui Poh; Alin Rai; Mulyoto Pangestu; Lois A Salamonsen; David W Greening
Abstract
Extracellular vesicles (EVs) are important mediators of embryo attachment and outgrowth critical for successful implantation. While EVs have garnered immense interest in their therapeutic potential in assisted reproductive technology by improving implantation success, their large-scale generation remains a major challenge. Here, we report a rapid and scalable production of nanovesicles (NVs) directly from human trophectoderm cells (hTSCs) via serial mechanical extrusion of cells; these NVs can be generated in approximately 6 h with a 20-fold higher yield than EVs isolated from culture medium of the same number of cells. NVs display similar biophysical traits (morphologically intact, spherical, 90-130 nm) to EVs, and are laden with hallmark players of implantation that include cell-matrix adhesion and extracellular matrix organisation proteins (ITGA2/V, ITGB1, MFGE8) and antioxidative regulators (PRDX1, SOD2). Functionally, NVs are readily taken up by low-receptive endometrial HEC1A cells and reprogram their proteome towards a receptive phenotype that support hTSC spheroid attachment. Moreover, a single dose treatment with NVs significantly enhanced adhesion and spreading of mouse embryo trophoblast on fibronectin matrix. Thus, we demonstrate the functional potential of NVs in enhancing embryo implantation and highlight their rapid and scalable generation, amenable to clinical utility.
Journal PROTEOMICS
ISSN 1615-9861
Published 12 Sep 2023
Volume
Issue
Pages e2300056 e2300056
DOI 10.1002/pmic.202300056
Type Journal Article
Sponsorship NHMRC: MRF2015523; PanKind Aust.: Innovation Grant