By Jacob Dykes
In Durham, a pioneering technology has been developed which is providing a solution to fundamental issues in tissue engineering and stem cell biology. The development of new innovative technology enables the advancement of the research and discovery process and scientific thinking as a whole. For example, it’s hard to conceive of a biomedical sphere untouched by the blessing of PCR or DNA sequencing. Technological advancements not only offer solutions to existing obstacles, they open up new avenues of research into previously inconceivable areas.
With the current levels of excitement in the research of stem cell biology, you could be forgiven for envisaging a utopian medical scenario where a process akin to science-fiction allows us to generate complex tissues in a Petri-dish, ready for transplantation into the damaged organism. The scientific community has speculated that the nature of stem cells, in their ability to self-renew and produce cell types of any lineage will eventually provide medical solutions to some of our most vilified tissue diseases.
Transitioning speculation to reality requires time, basic research and technology development. A novel product known as Alvetex has been developed by Reinnervate, a Durham University spin-out company, which enables a new routine approach to study stem cells and their ability to form tissues in the laboratory. The product unlocks the potential of stem cell differentiation by mimicking the natural three-dimensional (3D) microenvironment cells encounter in the body, enabling the formation of 3D tissue-like structures.
Cell behaviour, in general, is guided by the complex 3D microenvironment in which they reside. Dispersal of cell-cell interactions and architectural contacts across the surface of the cell are essential for regulating gene expression, the genetic mechanism by which cells change their character and behaviour. Recreation of this microenvironment in the laboratory is essential to studying physiologically relevant behaviour, and the differentiation process by which cells form new cell types. Alvetex is a micro-engineered 3D polystyrene scaffold into which cells can be impregnated for cultivation. Cells grow within a 200-micron thick membrane of the 3D material bathed in culture medium. The microenvironment enables cells to form 3D contacts with neighbouring cells, recreating the more natural interactions found in real tissues. Overall, this affects the structure and function of the cells, enabling them to behave more like their native counterparts, which in turn improves predictive accuracy when working with advanced cell culture models.
We can take progenitor cells from the skin of donors and produce… human skin… We can take cell lines from the intestine and reproduce the absorptive lining of the intestine. We can take neural progenitors and recapitulate 3D neural networks.”
Stefan Przyborski is a Professor of Cell Technology at Durham University and the founder of Reinnervate. He gave us an insight into his technology’s applications;
“We can take progenitor cells from the skin of donors and produce a full-thickness stratified human skin model (see image). We can take cell lines from the intestine and reproduce the absorptive lining of the intestine. We can take neural progenitors and recapitulate 3D neural networks to simulate aspects of nervous system function. Each of these models can be used to advance basic research, and extend our understanding of tissue development, and simulate aspects of disease.
“Such technology is underpinned by well established fundamental principles such as how cellular structure is related to function, which hails way back to Da Vinci himself. It is well known that if you get the structure and the anatomy correct than the physiology will start to follow.”
Alvetex technology has already been used in research that has led the publication of over 60 research papers in the field of tissue engineering and cancer biology. One particular group used the technology to successfully test drugs to prevent glioblastoma dispersal, an innovative application in brain oncology. Another has developed a 3D skin model to better study the development of metastatic melanoma, a persistently incurable invasive tumour of the skin. US scientists have used Alvetex on the International Space Station to study the formation of bone tissue in microgravity conditions.
The technology promises to be a cost-effective and ethical solution to current obstacles in cell culturing methods, producing better quality data relevant to man and reducing the need for animal models. Alvetex technology has offered a generational contribution to the process of tissue engineering research, yet the founder has higher ambitions;
“What I would like to see in the next few decades is the increased complexity of the tissues that stem cells can be used to generate. If you consider the structure of an organ, the complexity, arrangement and structural organisation of those cell populations, it is far from where we are today. Advances in technology at the interface between disciplines leads to new innovative ideas to solve problems and open up new opportunities.”
The development of stem cell research is an incremental process. We have to remain cautious given the potential of stem cell therapy to cause tumour formation, highlighting the need for more stringent models and controls. However, the clinical transplantation of cultured stem cells in bone and cornea repair demonstrates their enormous potential. Laboratory experiments have also demonstrated the potential of stem cells to produce kidney, pancreatic, liver, cardiac and muscle cells. It is hoped that continued research using more physiologically relevant technologies will increase the complexity of these tissues in the lab, and the diversity of their application.
Innovative technological advances play an important role in the process of biomedical science. Scientists at Durham are instrumental in the development of such new technologies that enable the process of new discoveries.
Photograph: Prof Stefan Przyborski, Durham University