Abstract
This study advances sustainable pharmaceutical research for endometriosis by aligning with the UN Sustainable Development Goals on health, gender equality, and responsible consumption in developing in vitro 3D cell culture models of endometriotic pathophysiology. Fibrosis is a key aspect of endometriosis, yet current models to study it remain limited, especially in 3D. This work aims to bridge the translational gap between in vitro fibrosis research and preclinical testing of non-hormonal drug candidates. When grown in a 3D matrix of sustainably produced silk protein functionalized with a fibronectin-derived cell adhesion motif (FN-silk), endometrial stromal and epithelial cells respond to transforming growth factor beta-1 (TGF-β1) in a physiological manner as probed at the mRNA level. For stromal cells, this response to TGF-β1 is not observed in spheroids, while epithelial cell spheroids behave similarly to epithelial cell FN-silk networks. Pirfenidone, an antifibrotic drug approved for the treatment of idiopathic pulmonary fibrosis, reverses TGF-β1-induced upregulation of mRNA transcripts involved in fibroblast-to-myofibroblast transdifferentiation of endometrial stromal cells in FN-silk networks, supporting the drug’s potential as a repurposed non-hormonal therapy for endometriosis. This study demonstrates how a sustainable approach – from project conceptualization to material selection – can be integrated into pharmaceutical research for women’s health.
Table of contents This paper presents in vitro 3D cell culture models of fibrosis in endometriosis. Endometrial stromal and epithelial cells cultured in networks of silk protein functionalized with a fibronectin-derived cell adhesion motif showed physiological-like fibrotic behavior. Pirfenidone was able to reverse fibrosis of endometrial stromal cells in vitro, demonstrating this model’s suitability as a screening tool for antifibrotic drugs for endometriosis.
Competing Interest Statement
No private study sponsors had any involvement in the study design, data collection, or interpretation of data presented in this manuscript. PL declares the following competing interests: she has consulted and received research grants on unrelated projects from Lipoid, Sanofi-Aventis Deutschland and DSM Nutritional Products Ltd. M.H. has shares in Spiber Technologies AB, a company that aims to commercialize recombinant silk. ST, MCB, LAG and MW declare no competing interests.
