Study On The Regulation Of The Fate Of NSCs And The Repair Of Spinal Cord Injury With The Recombinant TG2 Adenovirus Fibrin Scaffold

With the development of social economy,especially the popularization of automobiles,the incidence of spinal cord injury(SCI)has been increasing year by year in recent years.Moreover,due to the severe limb dysfunction caused by spinal cord injury,the impact on patients' various life activities is undoubtedly devastating,and it also brings various family and social problems.In recent years,the incidence of SCI has been increasing year by year,So exploring a method of repairing injured spinal cord will have great guiding significance for clinical treatment.Current research believes that after the spinal cord injury,the fracture and rupture of the upper and lower nerve conduction bundles due to the injury can directly lead to different degrees of functional impairments such as sensory and motor functions of the limbs below the level of the spinal cord injury.,Necrosis of local spinal cord tissue,forming a cavity inside the spinal cord tissue;In addition,the nerve cell regeneration ability is weak,and during the repair process,a large number of glial cells proliferate,which can form scar tissue and further hinder the regeneration of nerve fibers;The combined effect eventually leads to the necrosis and degeneration of neurons and nerve fibers.Fibrinogen,as a natural ECM material that can be taken from human blood,can be converted into fibrous fibrin under the action of coagulation factors.It has been widely used to construct a variety of tissue engineering scaffolds and drug sustained-release systems for transplantation to repair tissue damage.Neural stem cells(NSCs)are undifferentiated primitive cells that can produce neurons and glial cells in the nervous system;NSCs cultured in vitro have the potential for proliferation,self-renewal,and multidirectional differentiation.Neural stem cells(NSCs)exist in different parts of the central nervous system of adult mammals.NSCs can be differentiated into various target cells under appropriate conditions.Promote the proliferation and differentiation of endogenous stem cells,and establish a neural relay network locally to facilitate the repair of spinal cord injury.Transglutaminase2(TG2)can catalyze the crosslinking of covalent bonds within and between protein molecules.TG2 mainly exists in three forms,namely intracellular type,cell membrane type and secretory type(secreted in the form of microparticles).The main function of TG2 secreted into cells is to cross-link ECM molecules secreted by cells,such as fibronectin and laminin,into a three-dimensional network to provide a microenvironment for cell growth.In addition,TG2 can also cross-link growth factors with ECM,such as laminin,fibronectin,fibrin.The growth factor and the scaffold material are cross-linked through TG2 to construct a growth factor slow-release tissue engineering scaffold,which is used for transplantation to repair tissue damage.In this experiment,we embedded the TG2 gene-modified adenovirus together in fibrin gel to construct a fibrin scaffold that can slowly release the TG2 adenovirus.First,we observed the ability of the scaffold to slowly release TG2-Fibrin scaffold to slowly release TG2 adenovirus;then we cultured NSCs in vitro and used molecular biology methods to observe the regulation of NSCs fate and preliminary discussed the molecular mechanism;finally,we The scaffold carrying NSCs was co-transplanted into a rat model of spinal cord injury,and the effect of tissue engineering scaffold to promote functional repair of spinal cord injury rats was comprehensively evaluated.