Saltar al contenido
Merck
  • Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases.

Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases.

Science advances (2021-01-31)
Martin Trapecar, Emile Wogram, Devon Svoboda, Catherine Communal, Attya Omer, Tenzin Lungjangwa, Pierre Sphabmixay, Jason Velazquez, Kirsten Schneider, Charles W Wright, Samuel Mildrum, Austin Hendricks, Stuart Levine, Julien Muffat, Meelim Jasmine Lee, Douglas A Lauffenburger, David Trumper, Rudolf Jaenisch, Linda G Griffith
RESUMEN

Slow progress in the fight against neurodegenerative diseases (NDs) motivates an urgent need for highly controlled in vitro systems to investigate organ-organ- and organ-immune-specific interactions relevant for disease pathophysiology. Of particular interest is the gut/microbiome-liver-brain axis for parsing out how genetic and environmental factors contribute to NDs. We have developed a mesofluidic platform technology to study gut-liver-cerebral interactions in the context of Parkinson's disease (PD). It connects microphysiological systems (MPSs) of the primary human gut and liver with a human induced pluripotent stem cell-derived cerebral MPS in a systemically circulated common culture medium containing CD4+ regulatory T and T helper 17 cells. We demonstrate this approach using a patient-derived cerebral MPS carrying the PD-causing A53T mutation, gaining two important findings: (i) that systemic interaction enhances features of in vivo-like behavior of cerebral MPSs, and (ii) that microbiome-associated short-chain fatty acids increase expression of pathology-associated pathways in PD.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Seroalbúmina bovina, heat shock fraction, protease free, fatty acid free, essentially globulin free, pH 7, ≥98%
Sigma-Aldrich
Seroalbúmina bovina solution, 30% in DPBS, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
Triton X-100, for molecular biology
Sigma-Aldrich
Ácido retinoico, ≥98% (HPLC), powder
Sigma-Aldrich
N-Acetyl-L-cysteine, BioReagent, suitable for cell culture
Sigma-Aldrich
[Leu15]-Gastrin I human, ≥95% (HPLC)
Sigma-Aldrich
R-Spondin1 expressing 293T Cell Line, The R-Spondin1-Expressing 293T cell line produces RSPO1, a critical protein used to establish 3D organoid cultures from stomach, small intestine, colon, pancreas, and liver sources.
Millipore
Kit 3-plexado de perlas magnéticas MILLIPLEX® TGFß - Análisis inmunológico múltiple, for quantification of TGFß1, TGFß2 and TGFß3 in multiple species
Millipore
MILLIPLEX® Human Neuroscience Magnetic Bead Panel 1 - Neuroscience Multiplex Assay, allows quantitative multiplex detection of multiple analytes simultaneously