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Fibronectin‐induced ductal formation in salivary gland self‐organization model
Author(s) -
Farahat Mahmoud,
Kazi Gulsan A. S.,
Taketa Hiroaki,
Hara Emilio S.,
Oshima Masamitsu,
Kuboki Takuo,
Matsumoto Takuya
Publication year - 2019
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.78
Subject(s) - spheroid , biology , microbiology and biotechnology , matrigel , submandibular gland , fibronectin , salivary gland , organogenesis , ductal cells , chimera (genetics) , in vitro , anatomy , immunology , extracellular matrix , endocrinology , biochemistry , gene , immunohistochemistry
Background Recent advances in tissue regeneration approaches including 3D organoids, were based on various 3D organogenesis models. However, 3D models are generally technique‐sensitive and time‐consuming. Thus, we utilized an existing model of submandibular salivary gland (SMG) to modify a simple and highly reproducible in vitro 3D culture model of primary SMG cells self‐organization into a well‐developed cell spheroid inside Matrigel substrate. We used this model to observe the collective multicellular behavior during spheroid formation. Further, we applied various quantitative approaches including real‐time live imaging and immune histochemical image analysis to dissect the cellular dynamics during tissue patterning. Results On a time‐scale of hours, we observed marked size and shape transformations in the developed 3D spheroid which resulted in a spatially‐controlled growth differential from the canter to the periphery of the formed aggregates. Moreover, we investigated the effect of fibronectin (FN) on SMG cells self‐organization using our simplified culture model. Interestingly, we discovered a novel role of FN in inducing duct‐like elongation during initial stages of SMG bud formation. Conclusion This in vitro model provides an excellent tool for analyzing the intercellular dynamics during early SMG tissue development as well as revealing a novel role of FN in SMG ductal expansion.