Stem cell-based drug discovery assays targeting metabolic diseases

Research Project, 2014 – 2016

Animal studies are currently a prerequisite in the pre-clinical phase of the drug development process. However, the pharmacology industry reports [S.M. Paul Nature Rev. Drug Disc. 2010] that 88% of the by the emerging Coherent Anti-Stokes Raman Scattering (CARS) microscopy technique in living cells compounds showing promising pre-clinical results give undesirable responses in the human body, raising the need for more reliable and ethically acceptable assays. As an alternative, we propose to develop human in vitro tissues by growing stem cells in tissue-mimicking environments consisting of a mixing-induced two-component hydrogel (MITCH) based on two recombinant-engineered proteins with tunable (cell) interaction properties. They enable (i) long-term studies of relevant cells harvested from patients, rather than artificial cell lines; (ii) the formation of an immediate, biocompatible 3D environment which can be optimized at molecular level to promote native cell phenotype and functionality; and provide (iii) access to dynamic and detailed, single-cell drug response data by advanced and high-through put microscopy technology. As a first example, we will establish drug discovery assays for metabolic diseases by optimizing the molecular composition of the MITCH for adipose-derived stem cells from diabetes and obesity patients. Lipid storage will be monitored under the influence of insulin and drug molecules. Results will be compared with data from human tissue.

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