First aid kit of neural stem cells
Neural stem Cell Vesicles Promote tissue Repair
LifeSciencesToday based on University of Cambridge materials: Stem cells use “first aid kits" to repair damageAccording to a study published in the journal Molecular Cell (Cossetti et al., Extracellular Vesicles from Neural Stem Cells Transfer IFN-gamma via Ifngr1 to Activate Stat1 Signaling in Target Cells), neural stem cells – cells capable of developing into any type of nerve cells – create "mini-first aid kits" and transfer them to cells- targets.
Stem cells offer great opportunities in the restoration of affected cells in diseases such as multiple sclerosis, stroke or spinal cord injury, as they have the ability to develop into almost any type of cell. A new study shows that in addition to replacing the affected cells with healthy ones, stem cells have a therapeutic effect through a completely different mechanism.
A group of researchers led by scientists from the University of Cambridge has shown that stem cells "communicate" with cells by transferring molecules using fluid-filled bubbles called vesicles. The purpose of this interaction is to help other cells change the immune response that damages them.
Although scientists have long believed that by probing signals, migrating to certain areas of the body and performing complex reactions, stem cells can act like drugs, the molecular mechanism of this process has been demonstrated for the first time. His deeper understanding will help to find ways to maximize the effectiveness of stem cell-based therapy.
"These tiny bubbles in stem cells contain molecules such as proteins and nucleic acids that stimulate target cells and help them survive. They act as "mini-first aid kits," explains study leader Dr. Stefano Pluchino from the Stem Cell Institute of the University of Cambridge, associated with the Medical Research Council and the Wellcome Trust (Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute). "In fact, they reflect how stem cells react to an inflamed environment, like that observed in complex neural injuries and diseases, and transmit this ability to target cells. We believe that this helps the self-repair of damaged brain cells."
When neural stem cells (or neural progenitor cells, NCP) are injected into the blood mice with brain cell damage – such as in multiple sclerosis – have an amazing level of recovery. Scientists have suggested that this is because NKPS secrete molecules that control the immune system and, ultimately, suppress tissue damage or enhance their recovery.
The idea that stem cell-based therapy works only by replacing cells is challenged by the observation of constant intercellular molecular exchange between the graft and the host. Scientists have established the mechanism of cellular signaling by which neural stem cells/neural progenitor cells (NCPs) interact with the microenvironment through extracellular vesicles (EVs), and found out its molecular signature and function. They studied cytokine-regulated pathways that carry out protein and mRNA sorting in EVs, and described the induction of the interferon-gamma (IFN-gamma) pathway in NKPS exposed to proinflammatory cytokines. They showed that IFN-gamma, bound to EVs via Ifngr1 receptors, activates Stat1 in target cells. Finally, they showed that endogenous Stat1 and Ifngr1 in target cells are necessary to maintain Stat1 signaling activity through EV-associated IFN-gamma/Ifngr1 complexes. The study determines the mechanism of cellular signaling regulated by the EV IFN-gamma /Ifngr1 complexes, which the transplanted stem cells can use to interact with the host body's immune system. (Fig. Molecular Cell)A group of researchers from the UK, Australia, Italy, China and Spain showed that NCPs form vesicles in close proximity to the immune response zone and especially in response to the small protein cytokine interferon-gamma secreted by immune cells.
This protein has the ability to control both immune responses and internal brain repair programs and can alter cell function by regulating the activity of dozens of genes.
The data obtained by the researchers show that the trigger for the "activation" of a highly specific gene activation pathway in the NCP is interferon-gamma and that this protein binds to a receptor on the surface of vesicles. The released NCP vesicles are absorbed by target cells. In addition to the fact that target cells receive proteins and nucleic acids that help them in self-healing, they also receive interferon-gamma, which activates genes, located on the surface of vesicles.
To visualize vesicles moving in vitro between the NCP and target cells, researchers funded by the European Research Council and the Italian Society of Multiple Sclerosis MS (Italian MS Society) used electron microscopy and ultra-high resolution microscopy.
Rapid (2 hours) in vitro uptake of extracellular vesicles by target cells
through the plasma membrane. (Photo: CongJian Zhao)
"Our work highlights the surprising new role of stem cell–secreted vesicles in spreading the response to the surrounding microenvironment," adds Dr. Plucino. "This is a significant step forward in understanding the many levels of interaction between stem cells and the immune system, as well as a new molecular mechanism explaining how stem cell-based therapy works."
Portal "Eternal youth" http://vechnayamolodost.ru22.09.2014