Engineering an in vitro living pump

Growing human tissues in the laboratory has great potential in the search for new medical treatments and in the replacement of animal use in experiments. In this project we aim to grow heart tissue that within the laboratory can act as a living pump. The project is the first to make a functional three-dimensional mini-heart using human embryonic stem cells. The stem cells can be increased in number on demand and then can be persuaded to form heart cells (cardiomyocytes). So far scientists around the World have shown this to be possible but we want to go a step further. At Nottingham we can already create highly pure cardiomyocyte populations using genetic modification techniques. Now we will assemble these pure cardiomyocytes into devices that harness the contraction of the cells and create a system that can pump liquid. To achieve this ambitious aim we must form flexible tubes of polymers that have mechanical properties that allow cardiomyocytes to contract sheets of the polymer. When the cardiomyocytes relax, the polymer film must be sufficiently elastic to recover its original surface area. We will use micron scale patterning of molecules to create a chemical trail that forces the cardiomyocytes to organise into patterns that make the most efficient use of their contraction within populations of thousands of cells. The sheets of polymers and cells will be constructed into tubes with one-way valves and installed in a bioreactor that can measure fluid movement and the force of the contraction of the mini-heart.

A living fluid pump will be engineered from human embryonic stem cells. The pump will be the first component of a long-term strategy to build internal circulatory systems for in vitro engineered tissue, thereby bridging the major divide between in vitro engineered tissue and in vivo vascularised tissue. This feasibility study requires the fabrication of flexible tubes of a polymer with circumferential patterns of cardiomyocytes. The mechanical properties of the tubes will be fine tuned such that strength of contraction of the cardiomyocytes generates volume changes that can drive fluid movement and relaxation of the cells reverses the volume change. Uni-directional fluid flow will be measured within an in vitro bioreactor that can also provide pulsatile mechanical conditioning of the differentiated cardiomyocytes. Co-funded by EPSRC.