MassIVE MSV000089054

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Human and bovine endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues.

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Description

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 pathological changes associated with disease progression. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined cocktail 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 diseases states of the same tissue. Therefore, we envisioned that extracellular matrix derived from a native healthy tissue would be sufficient 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 the organoids cultured in Matrigel. Proteomic and Raman spectroscopy 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 the 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. [doi:10.25345/C52B8VF94] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Endometrium ; Organoid ; Uterus ; Hydrogels ; ECM

Contact

Principal Investigators:
(in alphabetical order) 		Dr Pradeep Tanwar, The University of Newcastle, Australia
Muhammad Fairuz Jamaluddin, University of Newcastle, Australia
Submitting User: MFJ003
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