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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - VESCEL (Vascular Engineering on chip using differentiated Stem Cells)

Teaser

Summary

In the VESCEL program we aim to develop innovative technologies enabling the use of differentiated human induced pluripotent stemcells (hiPSC) to engineer blood vessels in microfluidic chips that constitute realistic disease models for thrombosis and neurodegenerative (ND) diseases.

There are 6 sub-aims to be addressed for this overall aim to be achieved.

(1) Differentiating hiPSC into blood vessel tissue; (2) optimizing the culture conditions of hiPSC-derived vascular cells; (3) controlled engineering of blood vessel networks by culturing vascular cells in microfluidic chips; (4) integration of biosensors to monitor the state of the on-chip blood vessels; (5) applying the blood vessels on-chip in studying thrombosis; (6) applying the blood vessels on-chip in studying blood-brain barrier function.

The development of these complex and realistic disease models while having the potential to refine, reduce and (partly) replace existing animal models. Moreover, they will contribute significantly to our understanding of important vascular and neurological diseases.

Work performed

Work on all sub-aims has started in this first period, and the project is on track to successfully achieve the main aim. The highlights for achievements in the various sub-aims are listed below:

Implemented protocols for the differentiation of endothelial cells from hiPSC (sub-aim 1); first prototype of automated cell culture platform designed and produced (sub-aim 2); performed controlled angiogenesis experiments with endothelial cells in the microfluidic chips (sub-aim 3); developed first prototype of electrochemical nitric oxide sensor (sub-aim 4); visualized human blood thrombosis in a microfluidic vessel on-chip (sub-aim 5); performed initial brain-derived vascular cell culture on-chip (sub-aim 6).

This substantial scientific progress has already led to multiple publications (see \'Publications\' in report) in scientific journals, as well as accepted abstracts for major conferences in the field (e.g. microTAS, NanoBioTech, International Organ-on-Chip Sympsosium, Micro and Nanotechnology in Medicine Conference).

Final results

The current results of the project have demonstrated convincingly that hiPSC-derived cells can be used to engineer well-controlled vascular structures in microfluidic chips. hiPSC-derived vascular cells are person-specific, as well as a reproducible and indefinite source for cells of one specific donor, their integration in chips is a major accomplishment that will open the possibilities to apply the vessels-on-chips in biomedical and pharmaceutical science.

Moreover, the project has already led to significant technical innovation in the development of organ-on-chip systems in general, with highlights being the controlled 3D printing of vascular geometries, integration of on-line elcetrical biosensors for vascular barrier function, and a high level of control over 3D microvessel network formation by on-chip patterning of hydrogels.

For the second part of the project we expect a substantial integration of the developed protocols and technical innovations into hiPSC-based vessel-on-chip systems, as well as proof that these systems have unique added value in biomedical and pharmaceutical science.