Final Report Summary - SEM_SEM (SEcreted Membrane vesicles: role in the therapeutic plasticity of neural StEM cells)
Compelling evidence exists that somatic stem cell-based therapies protect the central nervous system from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis and stroke. It was first assumed that stem cells directly replace lost/damaged cells, but it has now become clear that they are able to protect the damaged nervous system through mechanisms other than cell replacement.
Here we have envisaged that major stem cell functions would result from highly sophisticated horizontal communication and we attribute a key role to the transfer of secreted membrane vesicles (EVs) from neural stem cells to target cells of the microenvironment. Using combination of cell and molecular biology, next generation deep-sequencing, computational analysis and bioinformatics tools we have demonstrated that stem cell EVs deliver functional IFN-gamma/Ifngr1 complexes to target cells, which may serve as a model of how stem cell grafts communicate with the host immune system. Helping to elucidate and fully define the cellular signaling that stem cells establish after transplantation will support an understanding of the definitive mechanisms underlying stem cell therapeutic plasticity.
Once evidence of the function of the molecules that are trafficked in stem cell vesicles is provided, it is not completely unrealistic to envisage a completely stem-cell-free (acellular) approach to those diseases that have been treated with stem cells so far, using stem cell vesicles. In situations where clinicians want to deliver stem cells with a specific function to a patient, working with EVs would make the function much easier to control.
Here we have envisaged that major stem cell functions would result from highly sophisticated horizontal communication and we attribute a key role to the transfer of secreted membrane vesicles (EVs) from neural stem cells to target cells of the microenvironment. Using combination of cell and molecular biology, next generation deep-sequencing, computational analysis and bioinformatics tools we have demonstrated that stem cell EVs deliver functional IFN-gamma/Ifngr1 complexes to target cells, which may serve as a model of how stem cell grafts communicate with the host immune system. Helping to elucidate and fully define the cellular signaling that stem cells establish after transplantation will support an understanding of the definitive mechanisms underlying stem cell therapeutic plasticity.
Once evidence of the function of the molecules that are trafficked in stem cell vesicles is provided, it is not completely unrealistic to envisage a completely stem-cell-free (acellular) approach to those diseases that have been treated with stem cells so far, using stem cell vesicles. In situations where clinicians want to deliver stem cells with a specific function to a patient, working with EVs would make the function much easier to control.