As part of a vitally important programme of research into stem cell medicine, the Evelyn Trust has funded Stefano Pluchino and his colleagues at the Pluchino Lab in Cambridge to investigate the mechanism of ‘communication’ from stem cells to immune cells. This communication could be important in repairing the damage caused by degenerative brain disease and spinal cord injuries.

“Recent advances in stem cell biology have raised hopes that brain diseases, such as multiple sclerosis, may be treated by stem cell medicines. The idea that stem cells work via cell replacement is challenged by the evidence of cellular signalling between the stem cells and the host immune system. This project has been able to show that extracellular neural RNAs (ribonucleic acids) are the vehicle by which stem cell grafts communicate with the host immune cells. We have also been working to identify the regulators of this intercellular communication. With our improved knowledge of basal stem cell functions we are now able to move forward with the development of innovative high impact therapeutics to help patients suffering from these very serious and debilitating illnesses,” explains Stefano Pluchino, University Reader in Regenerative Neuroimmunology and Honorary Consultant in Neurology at the University of Cambridge.

As a first step, Stefano’s team focussed on intercellular communication that works through the cell-to-cell transfer of extracellular membrane vesicles (EVs). Not only have they been able to show that this form of communication does exist for stem cells of the brain, but they have also been able to establish its ‘molecular signature’ and how exactly it works. EVs are the vehicle by which small non-coding nucleic acids (ncRNAs) – including microRNAs – are transferred and this is the mechanism by which transplanted stem cells ‘instruct’ neighbouring ‘target’ cells, affecting the expression of several genes and protein and so, ultimately the function of the target cells. They have also demonstrated the therapeutic potential of the transfer of individual small ncRNAs, carried by EVs. These discoveries also have significant potential for the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia, using an enzyme that can be communicated by EVs.

The Pluchino Lab is excited that they have proved that stem cell therapeutics can work by communicating with other cells, promoting the healing of the injured brain, rather than using stem cells to generate a new piece of tissue. 

“The long term perspective is very promising and we are now looking for more grant funding and biotech investors for a University of Cambridge spin out to take this work into the next phase,” adds Stefano.

You can read more about the ground-breaking work of the Pluchino Lab here: http://www.pluchinolab.org/PluchinoLab/Research.html