Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels

Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in synthetic hydrogels, which supports their growth. Thus, the synthetic hydrogels described here allow us to de-couple exogenous and nascent ECM to interrogate the role of ECM in organoid formation.

Authors

Institutions

Publication Details

Journal
Stem Cell Reports
Published
2024-12-12
DOI
https://doi.org/10.1016/j.stemcr.2024.11.006
Citations
20
Primary Topic
Inhalation and Respiratory Drug Delivery
Type
article
Field-Weighted Citation Impact
8.38

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels

Lindy K. Brastrom, Rosemary Spencer, Charlie J. Childs, Tristan Frum et al.
20 citations
Stem Cell Reports
Inhalation and Respiratory Drug Delivery
8.38
article

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels

Lindy K. Brastrom, Rosemary Spencer, Charlie J. Childs, Tristan Frum, Donia W Ahmed, Jason R. Spence, Darrell N. Kotton, Claudia Loebel, Madeline K. Eiken, Konstantinos–Dionysios Alysandratos, Eleanor M. Plaster, Orren Shachaf, Justin E. Levine, S. Pfeiffer
article en
20 citations

Abstract

Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in synthetic hydrogels, which supports their growth. Thus, the synthetic hydrogels described here allow us to de-couple exogenous and nascent ECM to interrogate the role of ECM in organoid formation.

Stem Cell ReportsVol. 20(1)
Boston Medical Center (US), University of Michigan (US), Michigan Medicine (US), The University of Texas at Austin (US)
National Science Foundation, Silicon Valley Community Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute
Openalex Percentile: Top 2%
Inhalation and Respiratory Drug Delivery
8.38
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.