Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to trans...Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.展开更多
The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a ...The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a ＇social＇ dimension to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane nanotube formation between neighbouring T cells. This is critically dependent on Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and cytosolic elements including active caspases can be observed to occur via these nanotubes. Nanotube formation and intercellular exchanges of death signals are defective in T lymphocytes from patients with autoimmune iymphoproliferative syndrome harbouring mutations in the Fas receptor. We conclude that nanotuhemediated exchanges constitute a novel form of intercellular communication that augments the propagation of death signalling between neighbouring T cells.展开更多
基金supported by the University of Urbino Carlo Bo(No.DR-473_2018)to WB。
文摘Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.
文摘The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a ＇social＇ dimension to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane nanotube formation between neighbouring T cells. This is critically dependent on Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and cytosolic elements including active caspases can be observed to occur via these nanotubes. Nanotube formation and intercellular exchanges of death signals are defective in T lymphocytes from patients with autoimmune iymphoproliferative syndrome harbouring mutations in the Fas receptor. We conclude that nanotuhemediated exchanges constitute a novel form of intercellular communication that augments the propagation of death signalling between neighbouring T cells.
