Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture
Summary: A long-standing constraint on organoid culture is the need to add exogenous substances to provide hydrogel matrix, which limits the study of fully human or fully native organoids. This paper introduces an approach to culture reconstituted mammary organoids without the impediment of exogenou...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-04-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221002212 |
| _version_ | 1818451759986638848 |
|---|---|
| author | Michael E. Todhunter Masaru Miyano Divya S. Moolamalla Aleksandr Filippov Rosalyn W. Sayaman Mark A. LaBarge |
| author_facet | Michael E. Todhunter Masaru Miyano Divya S. Moolamalla Aleksandr Filippov Rosalyn W. Sayaman Mark A. LaBarge |
| author_sort | Michael E. Todhunter |
| collection | DOAJ |
| description | Summary: A long-standing constraint on organoid culture is the need to add exogenous substances to provide hydrogel matrix, which limits the study of fully human or fully native organoids. This paper introduces an approach to culture reconstituted mammary organoids without the impediment of exogenous matrix. We enclose organoids in nanoliter-scale, topologically enclosed, fluid compartments surrounded by agar. Organoids cultured in these “microcontainers” appear to secrete enough extracellular matrix to yield a self-sufficient microenvironment without exogenous supplements. In microcontainers, mammary organoids exhibit contractility and a high-level, physiological, myoepithelial (MEP) behavior that has not been previously reported in reconstituted organoids. The presence of contractility suggests that microcontainers elicit MEP functional differentiation, an important milestone. Microcontainers yield thousands of substantially identical and individually trackable organoids within a single culture vessel, enabling longitudinal studies and statistically powerful experiments, such as the evaluation of small effect sizes. Microcontainers open new doors for researchers who rely on organoid models. |
| first_indexed | 2024-12-14T21:12:19Z |
| format | Article |
| id | doaj.art-11975e2bb4754e0d9d9633217366301e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T21:12:19Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-11975e2bb4754e0d9d9633217366301e2022-12-21T22:47:12ZengElsevieriScience2589-00422021-04-01244102253Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid cultureMichael E. Todhunter0Masaru Miyano1Divya S. Moolamalla2Aleksandr Filippov3Rosalyn W. Sayaman4Mark A. LaBarge5Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADepartment of Population Sciences, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADepartment of Population Sciences, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADepartment of Population Sciences, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADepartment of Population Sciences, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USADepartment of Population Sciences, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA; Corresponding authorSummary: A long-standing constraint on organoid culture is the need to add exogenous substances to provide hydrogel matrix, which limits the study of fully human or fully native organoids. This paper introduces an approach to culture reconstituted mammary organoids without the impediment of exogenous matrix. We enclose organoids in nanoliter-scale, topologically enclosed, fluid compartments surrounded by agar. Organoids cultured in these “microcontainers” appear to secrete enough extracellular matrix to yield a self-sufficient microenvironment without exogenous supplements. In microcontainers, mammary organoids exhibit contractility and a high-level, physiological, myoepithelial (MEP) behavior that has not been previously reported in reconstituted organoids. The presence of contractility suggests that microcontainers elicit MEP functional differentiation, an important milestone. Microcontainers yield thousands of substantially identical and individually trackable organoids within a single culture vessel, enabling longitudinal studies and statistically powerful experiments, such as the evaluation of small effect sizes. Microcontainers open new doors for researchers who rely on organoid models.http://www.sciencedirect.com/science/article/pii/S2589004221002212Cell BiologyStem Cells ResearchBioengineeringTissue Engineering |
| spellingShingle | Michael E. Todhunter Masaru Miyano Divya S. Moolamalla Aleksandr Filippov Rosalyn W. Sayaman Mark A. LaBarge Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture iScience Cell Biology Stem Cells Research Bioengineering Tissue Engineering |
| title | Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture |
| title_full | Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture |
| title_fullStr | Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture |
| title_full_unstemmed | Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture |
| title_short | Volume-constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture |
| title_sort | volume constrained microcontainers enable myoepithelial functional differentiation in highly parallel mammary organoid culture |
| topic | Cell Biology Stem Cells Research Bioengineering Tissue Engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221002212 |
| work_keys_str_mv | AT michaeletodhunter volumeconstrainedmicrocontainersenablemyoepithelialfunctionaldifferentiationinhighlyparallelmammaryorganoidculture AT masarumiyano volumeconstrainedmicrocontainersenablemyoepithelialfunctionaldifferentiationinhighlyparallelmammaryorganoidculture AT divyasmoolamalla volumeconstrainedmicrocontainersenablemyoepithelialfunctionaldifferentiationinhighlyparallelmammaryorganoidculture AT aleksandrfilippov volumeconstrainedmicrocontainersenablemyoepithelialfunctionaldifferentiationinhighlyparallelmammaryorganoidculture AT rosalynwsayaman volumeconstrainedmicrocontainersenablemyoepithelialfunctionaldifferentiationinhighlyparallelmammaryorganoidculture AT markalabarge volumeconstrainedmicrocontainersenablemyoepithelialfunctionaldifferentiationinhighlyparallelmammaryorganoidculture |