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Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues

journal contribution
posted on 2024-11-02, 22:12 authored by M. Jamaluddin, Arnab Ghosh, Aviraj Dnyandeo Ingle, Vipul BansalVipul Bansal
Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth–Holm–Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture–based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.

History

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

119

Number

e2208040119

Issue

44

Start page

1

End page

12

Total pages

12

Publisher

National Academy of Sciences

Place published

United States

Language

English

Copyright

Copyright © 2022 the Author(s). Published by PNAS.

Former Identifier

2006119205

Esploro creation date

2023-10-14

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