Contact: Louise Walsh
University of Cambridge
Stem cells use ‘first aid kits’ to repair damage
Stem cells hold great promise as a means of repairing cells in
conditions such as multiple sclerosis, stroke or injuries of the
spinal cord because they have the ability to develop into almost
any cell type. Now, new research shows that stem cell therapy can
also work through a mechanism other than cell replacement.
In a study published today in Molecular Cell, a team of researchers
led by the University of Cambridge has shown that stem cells
“communicate” with cells by transferring molecules via fluid filled
bags called vesicles, helping other cells to modify the damaging
immune response around them.
Although scientists have speculated that stem cells might act
rather like drugs – in sensing signals, moving to specific areas of
the body and executing complex reactions – this is the first time
that a molecular mechanism for this process has been demonstrated.
By understanding this process better, researchers can identify ways
of maximising the efficiency of stem-cell-based therapies.
Dr Stefano Pluchino from the Wellcome Trust-Medical Research
Council Cambridge Stem Cell Institute, who led the study, said:
“These tiny vesicles in stem cells contain molecules like proteins
and nucleic acids that stimulate the target cells and help them to
survive – they act like mini “first aid kits”.
“Essentially, they mirror how the stem cells respond to an
inflammatory environment like that seen during complex neural
injuries and diseases, and they pass this ability on to the target
cells. We think this helps injured brain cells to repair
Mice with damage to brain cells – such as the damage seen in
multiple sclerosis – show a remarkable level of recovery when
neural stem/precursor cells (NPCs) are injected into their
circulatory system. It has been suggested that this happens because
the NPCs discharge molecules that regulate the immune system and
that ultimately reduce tissue damage or enhance tissue repair.
The team of researchers from the UK, Australia, Italy, China and
Spain has now shown that NPCs make vesicles when they are in the
vicinity of an immune response, and especially in response to a
small protein, or cytokine, called Interferon-gamma which is
released by immune cells. This protein has the ability to regulate
both the immune responses and intrinsic brain repair programmes and
can alter the function of cells by regulating the activity of
scores of genes.
Their results show that a highly specific pathway of gene
activation is triggered in NPCs by IFN-gamma, and that this protein
also binds to a receptor on the surface of vesicles. When the
vesicles are released by the NPCs, they adhere and are taken up by
target cells. Not only does the target cell receive proteins and
nucleic acids that can help them self-repair, but it also receives
the IFN-gamma on the surface of the vesicles, which activates genes
within the target cells.
The researchers, who were funded by the European Research Council
and the Italian MS Society, used electron microscopy and
superresolution imaging to visualise the vesicles moving between
the NPCs and target cells in vitro.
“Our work highlights a surprising novel role for stem-cell-derived
vesicles in propagating responses to the environment,” added
Pluchino. “It represents a significant advance in understanding the
many levels of interaction between stem cells and the immune
system, and a new molecular mechanism to explain how stem-cell
Sent using Hushmail