Stem cell fractionation using interactions with artificial matrices

Lead Research Organisation: University of Manchester
Department Name: Chem Eng and Analytical Science


There has been a recent explosion in interest in and potential applications of stem cells. Their potential for therapeutic medical applications is particularly exciting, with the real prospect of growing replacement tissue and bone to overcome a wide variety of disease conditions. Stem cells also have an important role in diagnostics, and have already shown promise in drug discovery research. To date, the key limitation to the exploitation of stem cells has been their scarcity. Furthermore, even when it is possible to source stem cells, there is still the formidable task of purification and sorting of the usable cells from cells that have differentiated into unusable types. Presently, stem cells are labelled with markers and then sorted one-by-one using very expensive instruments. Despite the very high speed of modern cell sorters the relatively small numbers obtained and the addition of labelling reagents mean that these methods are not suitable for widespread application of stem cell therapy. Stem cells have yet to find global application, because of their rarity. This project proposes to change the current stem cell sorting methods from low throughput one-by-one techniques to very high throughput alternatives that will be capable of sorting millions of cells simultaneously. The key to this will be the design of a series of filters that behave as smart sieves. The stem cells will be poured through new filters that will recognise the cells by their shape, size, flexibility and their chemical signature, without the addition of any extra reagents. A set of filters will be assembled; one on top of the other, to allow rapid screening of a mixture that contains both the valuable wanted stem cells, alongside less useful cells. This research programme will focus on the design of these filter stages, and use cutting edge science and technology to generate a completely new approach to stem cell purification. Specialist techniques such as microfluidics, nanotechnology, rapid microstructure prototyping will be combined with the latest ideas in cell biochemistry and cell biorecognition to fulfil the primary objective of making it easier, cheaper and faster to harvest useful stem cells. The benefit to society will be huge, making the possibility of stem cell therapy a reality for everyone.

Planned Impact

There over 300 million people in the US, Europe and Japan who could potentially benefit from stem cell therapies. Current forecasts predict an increase in the stem cell market from $24.6bn in 2005 to $68.9bn in 2010, with regenerative medicine representing $10.7bn by 2010. The US and Europe are expected to remain the largest markets for stem cell therapies. As of 2005, there were 160 companies involved in the stem cell field, with 24 of these specialising in human or mouse ES cells. Many of these companies are small, but larger established companies are expected to enter the field as the technology progresses. Currently, there are no ES cell therapies available, directly reflecting the difficulties in isolating functional homogeneous populations of the desired somatic cell types. The provision of somatic cell types for drug testing is an emerging market with revenues of $3.6bn predicted by 2020. However, current manufacturing practice for the isolation of somatic cells relies on robotic culturing methods, resulting in high up-front costs (250k for hardware) and significant consumables and maintenance outlay. Therefore, technologies capable of reducing the cost of manufacturing and isolating specific cell types will significantly impact the barriers to entry for stem cell technologies and, ultimately, cellular therapies. A clear market for our product would be academic researchers, stem cell banks and regenerative medicine companies. The Business Communications Company (BCC) produced a report on the market potential of stem cell-related therapies andconcluded that blood-related technologies account for the largest share of the market. However, skin products (e.g. Appligraf) and cartilage/bone-related products (e.g. Carticel) have also contributed to strong growth. BCC predicted that other markets, including stem cells, will remain relatively small in the near-term as basic scientific and regulatory hurdles still need to be overcome, particularly in the isolation of specific cell types, an obstacle this proposal aims to overcome. Hardware sales represent very low income when compared to consumable sales and the focus of any business plan would be the sale of disposable cartridges for isolation of specific cell types to achieve continued sales revenue over several years. Essentially, this technology will allow the field to rapidly progress to pre-clinical/clinical trials with ES and/or adult stem cells, which is currently impossible due to the technological, regulatory and labour constraints of current methods. A further potential use of a stem cell purifying device is in the screening of blood samples to allow early detection of metastatic cancer cells. A screening device may provide a useful tool for both the early identification of metastasis and, more importantly, as a device for removing such cells from a patient's blood (akin to kidney dialysis). Furthermore, a device for isolation of cancer stem cells will be very useful for increasing our understanding of their biology in order to specifically target them in novel therapies. Two photon stereolithography is a technique that is just at the point of breaking out of the research laboratory and becoming a standard technique for prototyping of nanoscale polymer devices. We intend to use this technique in novel and commercially-exploitable ways to produce both the prototype devices and the means by which the cell filters can be mass produced. The main drawback with stereolithography of all kinds has long been the very slow build times, which limits the technique to prototyping and very small production runs. The technique of holographic lithography using holograms produced by two photon stereolithgraphy is novel (and risky), but if successful will enable the mass production of nanoscale devices. This is likely to be of major impact, as it could potentially replace injection moulding as a rapid polymer device production method.
Description Investigation of Nanoscribe materials for cavity formation for insulator materials 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Supply of materials and fabrication methodology for nanoinsulators
Collaborator Contribution Design of structures for nanoinsulators.
Impact None so far
Start Year 2012
Description Laboratory visits to Rensselaer Polytechnic Insitute, Troy, USA 
Organisation Rensselaer Polytechnic Institute
Country United States 
Sector Academic/University 
PI Contribution Dr Kate Meade visited RPI for 3 days where she attended lab meetings and toured the Institute. Best practice regarding 3D culture of cells was shared between the groups. Kate visited RPI to share information regarding 3D culture of cells. Kate was introduced to all lab members using variety of fibrous and gel-based scaffolds.
Start Year 2012
Description Cheltenham Science Festival, 8th June 2011 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Panel member in an hour-long session entitled "Stem Cells" where the basic ideas behind the project were presented. After presentations from the panel members, took part in a panel question and answer session fielding questions from a large (200+) audience.

Major UK science festival.

Audience were generally supportive of stem cell therapies.
Year(s) Of Engagement Activity 2011
Description Presentation at the Royal Society Summer Exhibition 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Kate Meade is presenting the work developed as part of this project to support the 'Sweet Complexity' focus at the Royal Society Summer Exhibition in London in July.

The sugar-binding surfaces developed as part of this project are used as an example of sugar-modified biomaterials as part of the glycoscience event at the Royal Socieity Summer Exhibition. Kate Meade (PDRA on this grant) will be present at the event and presenting a mini-experiment demonstrating how sugars influence signalling factor diffusion during differentiation.

Fruther coollaboration requests received.
Year(s) Of Engagement Activity 2013
Description Stall at Science Spectacular Event as part of Manchester Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation workshop facilitator
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The technology underlying this project formed part of the interactive display at the festival.

Increased awareness amongst public of stem cell therapies and limitations of the technique.
Year(s) Of Engagement Activity 2012