cell culture with tissue ecm in a microfluidic chip

Microfluidic gastrointestinal tissue-mimetic microenvironments for long-term organoid culture

Abstract

“Matrigel, a mouse tumor extracellular matrix protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to-batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal tissue-derived extracellular matrix hydrogels are suitable substitutes for Matrigel in gastrointestinal organoid culture. We found that the development and function of gastric or intestinal organoids grown in tissue extracellular matrix hydrogels are comparable or often superior to those in Matrigel. In addition, gastrointestinal extracellular matrix hydrogels enabled long-term subculture and transplantation of organoids by providing gastrointestinal tissue-mimetic microenvironments. Tissue-specific and age-related extracellular matrix profiles that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that extracellular matrix hydrogels derived from decellularized gastrointestinal tissues are effective alternatives to the current gold standard, Matrigel, and produce organoids suitable for gastrointestinal disease modeling, drug development, and tissue regeneration.

Microfluidic cell culture with tissue ecm matrix hydrogel

Microfluidic system for dynamic culture and mass production of GI organoids in ECM hydrogels. Schematic illustration of (a) chip design and (b) the working principle of the microfluidic system for dynamic culture using a rocker. Mass production of (c) gastric and (d) intestinal organoids in GI tissue-derived ECM hydrogels using the microfluidic system. Gastric and intestinal organoids were observed at day 5 and day 6 in the culture, respectively (scale bars = 1 mm). Representative images from three independent experiments are shown in (c) and (d). Reproduced under Creative Commons Attribution 4.0 International License from Kim, S., Min, S., Choi, Y.S. et al. Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids. Nat Commun 13, 1692 (2022).


Figures and the abstract are reproduced from Kim, S., Min, S., Choi, Y.S. et al. Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids. Nat Commun 13, 1692 (2022). https://doi.org/10.1038/s41467-022-29279-4 under Creative Commons Attribution 4.0 International License.


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