Research at the University of Manchester has identified networks of proteins that control the fate of our body’s stem cells, findings that could aid progress towards new disease therapies.

Extracellular matrix networks control stem cell fate // Image by Adam Byron

Stem cells have the amazing ability to develop into different types of cells of the body, such as blood cells, muscle cells or brain cells. Remarkably, stem cells can also regenerate, essentially renewing themselves an unlimited number of times.

This unique set of abilities makes stem cells very important potential tools for the treatment of a range of diseases, including cardiovascular, inflammatory and neurological diseases. If stem cells could be instructed to develop into specific cell types that are damaged or destroyed in a diseased patient, then the damaged tissue could be replaced, which holds great promise for treating diseases. Such cell-based therapies form the basis of the relatively new field of regenerative medicine and could lead to huge benefits for patients.

Much remains to be understood about how stem cells grow, survive and develop. Scientists need this knowledge, not only to work out how the human body develops and functions normally, but also to predict and control how stem cells may behave when they are used as therapeutics to treat disease.

To move towards this understanding, researchers must first work out exactly why stem cells sometimes regenerate happily and sometimes lose their self-renewing ability and develop (or differentiate) into different cell types.

It is known that the protein networks surrounding stem cells – the extracellular matrix in which cells live – play a critical role in determining the fate of stem cells. But it is not clear precisely how the special properties of stem cells are regulated by their microenvironment or how they can be carefully controlled for use as potential clinical therapies.

This led a team of researchers at the University of Manchester to investigate which extracellular matrix proteins were involved in maintaining undifferentiated, self-renewing stem cells.

A collaborative effort between the research teams of Professor Sue Kimber and Professor Martin Humphries at the University of Manchester combined expertise in stem cell biology, regenerative medicine, cell adhesion and proteomics to tackle this challenge. I was part of the Humphries’ lab group that analysed the component parts of the extracellular matrix networks using proteomics.

Our research, which was published online in the Journal of Biological Chemistry yesterday, characterised the composition of the extracellular matrix secreted by cells that can support the self-renewal of stem cells. These protein networks were compared to the extracellular matrix produced by cells that are unable to support stem cell self-renewal.

This will bring the clinical use of stem cells in tissue regeneration that bit closer.

This approach identified several extracellular matrix molecules that facilitate stem cell self-renewal. Interestingly, it also revealed that the right molecules must work together, like an interconnected web surrounding the stem cells, to control their fate effectively. Together, these molecules act as signals that could direct stem cells to restore tissue function.

These insights into stem cell growth are valuable for understanding how stem cells can be grown under defined conditions. Long-term growth of stem cells on defined substrates will allow scientists to develop robust cell-based therapies that could be used in patients. This will bring the clinical use of stem cells in tissue regeneration that bit closer.

Funding: This work was supported by the Biotechnology and Biological Sciences Research Council, the Northwest Regional Development Agency, the Wellcome Trust and the Republic of Turkey Ministry of National Education.

Citation: D Soteriou, B Iskender, A Byron, JD Humphries, S Borg-Bartolo, M-C Haddock, MA Baxter, D Knight, MJ Humphries, SJ Kimber, Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance. J. Biol. Chem. 288, 18716–18731 (2013). HTML | PDF | PubMed

28 June 2013 //
Update: The paper was published in today’s issue of the Journal of Biological Chemistry, and the citation was updated accordingly.

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