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The Study Of Tracer And Magnetic Field On Neural Stem Cells

Posted on:2020-08-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:D LiFull Text:PDF
GTID:1360330611955292Subject:Biology
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Stem cells,as a class of cells with self-renewal and differentiation potential,mainly include embryonic stem cells(ESCs)and adult stem cells.At present,stem cells have been widely used in tissue engineering,medical regeneration,cancer research,and treatment of neurodegenerative diseases.Research on stem cells is an attractive topic in the field of biomedicine.The subject of this study are neural stem cells(NSCs)which are kinds of pluripotent stem cells that are present in adult tissues and can usually be induced to differentiate into neurons,astrocytes,and oligodendrocytes.Currently,NSCs have been used to treat a variety of neurodegenerative diseases and non-neurodegenerative diseases including Parkinson's syndrome(PD),Huntington's disease(HD)and Alzheimer's disease(AD).Although stem cell therapy shows great potential,there are still some problems to be solved in its application,such as low survival of transplanted stem cells and uncontrollable differentiation.Accurately tracking the survival,migration,and function of stem cells after transplantation in vivo is critical to understanding the physiological functions of stem cells and their applications.Therefore,the development of biocompatible stem cell tracers is critical for stem cell applications.It has been reported that different nanomaterials have been applied to the tracer study of stem cells,including the superparamagnetic iron oxide nanoparticles(SPIO).While these nanomaterials are excellent candidates for stem cell tracers,they may affect physiological functions of stem cells,including proliferation and differentiation.The application of these nanomaterials as stem cell tracers requires assessment of stem cell effects,including biosafety,self-renewal and directed differentiation testing.One of aims of this project is SPIO which is mainly composed of iron oxide molecules and capsid,which was emerged in the end of the last century.SPIO has been used in a variety of biomedical fields such as clinical tracing,drug delivery,cancer diagnosis and treatment.As a commonly used physical control method,magnetic field has also been used in many fields of application.Among them,in the field of biomedicine,magnetic fields are usually combined with SPIO for drug delivery and Magnetic Resonance Imaging(MRI).In particular,magnetic fields have also been reported to have a certain regulatory effect on the proliferation,differentiation,and migration of stem cells.Another aim of this study is the ring metal iridium(?)complex,which is an excellent fluorescent material due to its excellent physical and chemical properties including high quantum yield,large Stokes shift,low autofluorescence,and good light stability,so more and more attention has been paid to it.It has a wide variety of ruthenium complexes and is an excellent one-photon and two-photon probe,and has been successfully used in experimental studies such as specific labeling of organelles and live tracing of animals.This study prepared two tracers for stem cell transplantation-SPIO and Ir(MDQ)2acac nanospheres.First of all,we tested the inoculation,metabolism and biocompatibility of SPIO and NSCs and found that SPIO can successfully enter NSCs,and mainly stay in the lysosomal,and has good biocompatibility with cells.At the same time,its metabolism after entering the cell was slow,and there was still a large amount of retention in the cells during the 11-day test.In addition,the research also found that SPIO itself can regulate the proliferation,migration and metabolism of NSCs;the magnetic field will also have a certain impact on the proliferation and migration behavior of NSCs;when both are applied to NSCs,the two will create complex interactions that affect the proliferation and migration behavior of NSCs.Transcriptomics studies have also found that SPIO has less effect on the transcription of NSCs,while magnetic fields have a greater impact.In vivo tracing of Ir(MDQ)2acac nanosphere-labeled NSCs revealed that the material has good biocompatibility with cells and has excellent one-photon and two-photon imaging in vitro.At the same time,the labeled NSCs were transplanted into nude mice,and the fluorescent signal could be traced for up to 21 days.The research on this topic provides two safe candidate tracers for the tracing of stem cell transplantation,and on the other hand,it also deepens the understanding of the mechanism of using SPIO and magnetic field to regulate NSCs,which will provide broader prospects for stem cell applications.
Keywords/Search Tags:Neural stem cells, Superparamagnetic iron oxide nanoparticles, Magnetic field, Ir?MDQ?2acac nanosphere
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