Organotypic co-culture systems

There is an increasing demand for better and more meaningful in-vitro test and model systems in biomedical research. Since pre-clinical data obtained from animal models in particular can often not be extrapolated to the human condition, it is expedient to validate at least fundamental biological parameters in human cells with organotypic systems.

The processes that are associated with cell transplantations, such as paracrine interactions, can be simulated by means of co-culture systems, where stem cells are co-cultured in vitro with the target tissue. These systems offer possibilities for analysis and evaluation both in basic research and in the development of innovative cell-based clinical applications.

There is an increasing demand for better and more meaningful in-vitro test and model systems in biomedical research. Since pre-clinical data obtained from animal models in particular can often not be extrapolated to the human condition, it is expedient to validate at least fundamental biological parameters with human cells in organotypic systems. In particular in the field of personalized medicine, there is an urgent need for investigations into cell-tissue interactions in the context of cell transplantations to understand the impact and fate of the donor cells.

The frequently observed benefit of a treatment with stem cells seems to depend to a considerable degree on paracrine interactions between the stems cells and the recipient’s tissue and immune system. These processes can be simulated by means of co-culture systems, where stem cells are co-cultured in vitro with the target tissue. Two different experimental systems are available for this:

I. To study direct interactions between cells and tissue, these are co-cultured, so that actual cell-cell contacts can be analyzed.

II. To enable investigation of paracrine interactions via soluble growth factors, cells and tissue are cultured in a two-chamber system with a porous membrane. This allows for signal crosstalk of stem cells and tissue cells, which can be studied in detail by analyzing the culture medium.

Recently published experimental data have already demonstrated that xenogenic co-culture of different adult stem cell populations with rat brain biopsies induces neuronal differentiation of the stem cells, enabled by the release of growth factors by both stem cells and brain cells (1). In addition, the co-culture was found to cause an increased release of immunomodulatory and angiogenic cytokines by the stem cells. This is beneficial in the context of cell-based therapeutic strategies, as the transplanted cells can expedite wound healing and/or angiogenesis. 

An adaptation of the system to other tissue and cell types is principally possible, although each new tissue requires additional development and adjustment steps. Numerous techniques, methods, and tools have been developed for this at the Fraunhofer EMB and, thanks to many years of experience, scientists of this research institution have managed to successfully culture even critical tissue and organs, such as heart and liver. Furthermore, besides stem and progenitor cells they can meanwhile cryoconserve also tissue samples (e.g. skin), so that the availability of these systems can be guaranteed independently of the delivery of donor tissue.

These co-culture models thus offer possibilities for analysis and evaluation that may give valuable insights both in basic research and in the development of innovative cell-based clinical applications. 

Literature:

(1) Petschnik AE, Fell B, Tiede S, Habermann JK, Pries R, Kruse C, Danner S. A novel xenogenic co-culture system to examine neuronal differentiation capability of various adult human stem cells. PLoS One. 2011;6(9):e24944.