Madin-Darby canine kidney cells

[8] They based this conclusion on the fluid transport activities of monolayers formed of MDCK cells, the presence of microvilli on their apical (upper) surface, and their ability to self-organize, when grown in 3D, into hollow spheres.

In 1982 Mina Bissell and colleagues showed that MDCK monolayers responded to the addition of a collagen overlay (dubbed a "sandwich culture") by proliferating and forming hollow tubules.

However, they could be induced to break cell-cell contacts and become elongated and motile after exposure to a "scatter factor" that was secreted by mesenchymal cells such as Swiss 3T3 fibroblasts.

[13] During the same period in the mid 1980s, a monoclonal antibody was reported by the group of Walter Birchmeier to disrupt cell-cell contacts and alter the front-rear polarity of cells in culture.

Epithelial cells are typically nonmotile, but can become motile by inhibiting cell-cell junctions or by addition of growth factors that induce scattering.

Beyond that immediate paradox, a crucial connection was forged between the acute induction of cell motility in 2D culture by the "scatter factor", and its impact on the spatial organization adopted by tissues in 3D.

This connection remains significant as a link between precisely defined mechanisms of cell motility in 2D and complex rearrangements in 3D whose regulation is yet to be understood fully.

In support of this model, Mostov and colleagues have identified the effects of HGF on MDCK acini as eliciting a partial transition from epithelial to mesenchymal cell phenotypes.

[28][29] Their studies have shown that branching morphogenesis requires the Erk transcription factor, downstream of the mitogen activated protein kinase cascade, a well-defined signal transduction pathway implicated in cell motility and proliferation.

[30] The precise cell motility machinery responsible for MDCK branching morphogenesis has not been specified by the Mostov group, beyond the requirement for a signaling protein involved in regulating the small GTPase Rho.

Combined with observations from the Mostov group, this work confirmed that cell polarity is indispensable for MDCK acinar homeostasis as well as migratory behaviors during branching morphogenesis.

Typical colonies formed by Madin-Darby canine kidney cells when cultured in typical 2D format on plastic. Cells grow as tight colonies thanks to their cell-cell junctions, a hallmark of cells of epithelial origin.
Branching morphogenesis over two days by Madin-Darby canine kidney cells in response to hepatocyte growth factor (HGF). Images were acquired by fluorescence confocal microscopy, showing the structural protein actin, which highlights cell borders. Left: multicellular hollow spheres of cells, termed acini, were grown in 3D culture. Right: after 2 days of treatment with HGF cells have formed multiple branches.