Photo-Cross-linked Gelatin Methacryloyl Hydrogels Enable the Growth of Primary Human Endometrial Stromal Cells and Epithelial Gland Organoids.
Autor: | Salisbury E; Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K., Rawlings TM; Division of Biomedical Sciences, Reproductive Health Unit, Clinical Science Research Laboratories, Warwick Medical School, University of Warwick and Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, U.K., Efstathiou S; Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K., Tryfonos M; Division of Biomedical Sciences, Reproductive Health Unit, Clinical Science Research Laboratories, Warwick Medical School, University of Warwick and Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, U.K., Makwana K; Division of Biomedical Sciences, Reproductive Health Unit, Clinical Science Research Laboratories, Warwick Medical School, University of Warwick and Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, U.K., Fitzgerald HC; The Ritchie Centre, Hudson Institute of Medical Research, Clayton VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Clayton VIC 3168, Australia., Gargett CE; The Ritchie Centre, Hudson Institute of Medical Research, Clayton VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Clayton VIC 3168, Australia., Cameron NR; Department of Materials Science and Engineering, Monash University, Clayton, Victoria 3800, Australia.; School of Engineering, University of Warwick, Coventry CV4 7AL, U.K., Haddleton DM; Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K., Brosens JJ; Division of Biomedical Sciences, Reproductive Health Unit, Clinical Science Research Laboratories, Warwick Medical School, University of Warwick and Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, U.K., Eissa AM; Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.; Department of Polymers, Chemical Industries Research Division, National Research Centre, El Bohouth St. 33, Dokki, Cairo Giza 12622, Egypt.; School of Life Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, U.K. |
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Jazyk: | angličtina |
Zdroj: | ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 Jul 31; Vol. 16 (30), pp. 39140-39152. Date of Electronic Publication: 2024 Jul 18. |
DOI: | 10.1021/acsami.4c08763 |
Abstrakt: | In vitro three-dimensional (3D) models are better able to replicate the complexity of real organs and tissues than 2D monolayer models. The human endometrium, the inner lining of the uterus, undergoes complex changes during the menstrual cycle and pregnancy. These changes occur in response to steroid hormone fluctuations and elicit crosstalk between the epithelial and stromal cell compartments, and dysregulations are associated with a variety of pregnancy disorders. Despite the importance of the endometrium in embryo implantation and pregnancy establishment, there is a lack of in vitro models that recapitulate tissue structure and function and as such a growing demand for extracellular matrix hydrogels that can support 3D cell culture. To be physiologically relevant, an in vitro model requires mechanical and biochemical cues that mimic those of the ECM found in the native tissue. We report a semisynthetic gelatin methacryloyl (GelMA) hydrogel that combines the bioactive properties of natural hydrogels with the tunability and reproducibility of synthetic materials. We then describe a simple protocol whereby cells can quickly be encapsulated in GelMA hydrogels. We investigate the suitability of GelMA hydrogel to support the development of an endometrial model by culturing the main endometrial cell types: stromal cells and epithelial cells. We also demonstrate how the mechanical and biochemical properties of GelMA hydrogels can be tailored to support the growth and maintenance of epithelial gland organoids that emerge upon 3D culturing of primary endometrial epithelial progenitor cells in a defined chemical medium. We furthermore demonstrate the ability of GelMA hydrogels to support the viability of stromal cells and their function measured by monitoring decidualization in response to steroid hormones. This study describes the first steps toward the development of a hydrogel matrix-based model that recapitulates the structure and function of the native endometrium and could support applications in understanding reproductive failure. |
Databáze: | MEDLINE |
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