Corneal endothelium defects are one of the leading causes of blindness worldwide.The actual treatment is transplantation,which requires the use of human cadaveric donors,but it faces several problems,such as global sh...Corneal endothelium defects are one of the leading causes of blindness worldwide.The actual treatment is transplantation,which requires the use of human cadaveric donors,but it faces several problems,such as global shortage of donors.Therefore,new alternatives are being developed and,among them,cell therapy has gained interest in the last years due to its promising results in tissue regeneration.Nevertheless,the direct administration of cells may sometimes have limited success due to the immune response,hence requiring the combination with extracellular mimicking materials.In this review,we present different methods to obtain corneal endothelial cells from diverse cell sources such as pluripotent or multipotent stem cells.Moreover,we discuss different substrates in order to allow a correct implantation as a cell sheet and to promote an enhanced cell behavior.For this reason,natural or synthetic matrixes that mimic the native environment have been developed.These matrixes have been optimized in terms of their physicochemical properties,such as stiffness,topography,composition and transparency.To further enhance the matrixes properties,these can be tuned by incorporating certain molecules that can be delivered in a sustained manner in order to enhance biological behavior.Finally,we elucidate future directions for corneal endothelial regeneration,such as 3D printing,in order to obtain patient-specific substrates.展开更多
基金funded by the Government of Catalonia(2017 SGR 708)the Spanish Ministry(Ramòn y Cajal fellowship(RYC2018-025977-I)project RTI2018-096088-J-100(MINECO/FEDER)),and predoctoral fellowship from Generalitat de Catalunya(FI).
文摘Corneal endothelium defects are one of the leading causes of blindness worldwide.The actual treatment is transplantation,which requires the use of human cadaveric donors,but it faces several problems,such as global shortage of donors.Therefore,new alternatives are being developed and,among them,cell therapy has gained interest in the last years due to its promising results in tissue regeneration.Nevertheless,the direct administration of cells may sometimes have limited success due to the immune response,hence requiring the combination with extracellular mimicking materials.In this review,we present different methods to obtain corneal endothelial cells from diverse cell sources such as pluripotent or multipotent stem cells.Moreover,we discuss different substrates in order to allow a correct implantation as a cell sheet and to promote an enhanced cell behavior.For this reason,natural or synthetic matrixes that mimic the native environment have been developed.These matrixes have been optimized in terms of their physicochemical properties,such as stiffness,topography,composition and transparency.To further enhance the matrixes properties,these can be tuned by incorporating certain molecules that can be delivered in a sustained manner in order to enhance biological behavior.Finally,we elucidate future directions for corneal endothelial regeneration,such as 3D printing,in order to obtain patient-specific substrates.