In vitro models closely mimicking human liver functions are of key importance during drug development since hepatotoxicity of new drug candidates is a major problem. This is mainly due to the low predictive strength of the classical animal based safety studies and current hepatic in vitro models. The latter fail to maintain the metabolic liver functions and have a short lifespan.
Our group offers a methodology that could improve the functionality of hepatic cell cultures:
Decellularized liver matrix as cultivation scaffold and substratum
With the present methodology, native 3D decellularized liver matrix (DLM) is obtained in less than one hour by sequential perfusion of liver with carefully selected detergents:
- major liver ECM proteins (laminin, collagen I and IV, fibronectin) are preserved,
- liver ECM-bound growth factors are present,
- liver vasculature remains intact.
When used as cell cultivation scaffold or substratum, the DLM could improve cell function and viability by promoting a higher level of cell organization in an adequate hepatic microenvironment. Indeed, it is already known that the restoration of in vivo-like interactions between hepatocytes and extracellular matrix (ECM) and 3D-cultivation are important determinants of hepatocyte survival and preservation of phenotypic functions.
- the closest replica of in vivo-like hepatic microenvironment,
- native 3D backbone made of essential liver proteins and growth factors providing structural and biological stimuli to promote cell engraftment and maintence of metabolic functions,
- vasculature capable of withstanding fluid flows and enabling incorporation of the DLM into a bioreactor,
- repopulation with primary cells, hepatic cell lines and their hepatic progeny feasible, with > 99% of cells remaining viable after reseeding,
- lyophilized form for coating of culture dishes available,
- methodology applicable to different species.
DLM could aid in developing phenotypically stable hepatic in vitro models for safety and/or efficacy testing. Therefore, high impact is expected on:
- the cosmetic industry, where animal testing and marketing bans became final in March 2013, irrespective of the availability of alternative non-animal tests,
- the pharmaceutical industry, where in vitro methods become key for early decision making in the drug development process due to their speed, high throughput and cost-effectiveness,
- the chemical industry, where safety testing under REACH is associated with substantial financial costs and high animal consumption.
What are we looking for?
- Setting up joint R&D projects with industrial and/or academic partners to further develop DLM as a bioengineering and cell cultivation platform for use in e.g. toxicological assays,
- Providing expertise in the area of organ decellularization methodologies on the fee-for-service or collaborative basis.
Customer-tailored solutions are also discussable.
Interested parties can contact:
- Mrs. Manon Vivier
- [T]: +32 (0)2 477 45 19