Functionalized substrate to manipulate cell function and differentiation

Abstract

The invention relates to a scaffold for steering cells into a predetermined direction of cell functionality, preferably a cell differentiation scaffold for steering cells into a predetermined direction of cell differentiation. The scaffold comprises a polydimethylsiloxane (PDMS)-, or rubber-, or silicone-based polymeric surface, and one or more cell functionality-inducing stimuli, preferably one or more cell differentiation-inducing stimuli, coupled to the polymeric surface.

Description

FIELD OF THE INVENTION[0001]The present invention generally relates to the field of biotechnology, bioinformatics and related arts. More particularly, the present invention relates to a substrate or scaffold for steering cells into a predetermined direction of cell functionality and also to a culturing unit comprising such substrate or scaffold. The invention also pertains to an in vitro method of producing a cell culture, tissue or organ by steering cells into a predetermined direction of cell functionality. The present invention further relates to a non-transitory storage medium storing instruction that are executable by a digital processing device to perform the aforementioned method. The present invention further relates to a computer program comprising program code means for causing a digital processing device to perform the aforementioned method, when the computer program is run on a digital processing device. The present invention further relates to a system for performing th...

AI Technical Summary

Benefits of technology

[0013]The substrate, which preferably comprises or is a scaffold, is for steering cells into a predetermined direction of cell functionality. Such steering can typically be done during cultivation or culturing of cells. The substrate includes an elastomeric material to which the one or more cell functionality-inducing stimuli are coupled. The stimuli are for aiding or causing the steering. This implies that the stimuli are preferably at least present at an elastomer surface of the elastomer material to be available for such steering during cultivation of cells. The presence of the stimuli at the elastomeric material surface provides a controlled environment in that the steering can take place at or near the surface of the elastomeric material.

[0025]With the present invention a robust method is provided that can be controlled so that cells may reproducibly adopt a particular cellular behavior that is less dependent from existing knowledge and / or experience as known methods. The method of the present invention allows to directly determine whether the cells indeed react to the culture conditions determined in step (a) in the expected manner. Therefore, in the first step (a) culture conditions are determined that are known or at least assumed to steer a particular cell (i.e. cell type) towards a desired cell behavior. In step (b), cells of the same cell type as in (a) are cultivated to provide a cell culture. Pathway activity is inferred in step (c). Comparing the inferred activity with the activity selected so to control cell behavior in a first predetermined manner (i.e. the selected activity) of the at least one first signaling pathway during cultivation allows to monitor cell response on the level of the cell culture, monitor progress of the cell culture to acquire a particular cellular behavior, confirm or decline that the cell culture has acquired the desired cell behavior or steer into the desired direction, and the like. More particularly, the present invention allows to draw conclusions with regard to cell behavior by preferably quantitatively inferring activity of signaling pathway(s) that mediate the respective cell behavior. For example, differentiation of stem cells to certain tissue may involve activation of one or more pathways. Inferring activity of said one or more pathways allows to safeguard that the respective signaling pathway(s) is / are indeed active. Information, in particular quantitative information, on the pathway activity can be advantageously used for the purposes of the present invention as a basis for minimizing deviations from the desired cell behavior so that cell behavior can be precisely controlled, and cells can be steered into the desired direction. The present invention thus provides a method which enables cell cultivation in a more controllable fashion than it is possible with existing methods.

Problems solved by technology

A disadvantage of known techniques, whether carried out in conventional culture systems or microfluidic devices, is that they rely primarily on control of culture conditions.

Images