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The Application Of Mesenchymal Stem Cell With New Type Of Biological Material/growth Factor In The Skin Wound Repairment

Posted on:2018-04-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:1364330518965041Subject:Human Anatomy and Embryology
Abstract/Summary:PDF Full Text Request
Skin is the first barrier of human body,which attracted a wide spread attention on its wound healing.The healing of large area and refractory wounds can hardly be repaired by the proliferation and migration of epithelial cells in wound edge,it usually need manual intervention.Therefore,stem cell,biological materials,cytokine therapy and other treatment means were applied to the skin wound.Mesenchymal stem cells(MSC)is an important member of the stem cell family,because of its multi-directional differentiation ability,it has become an ideal source of seed cells for treating skin wounds.Mesenchymal stem cells includes bone marrow mesenchymal stem cells,umbilical cord mesenchymal stem cells,adipose derived mesenchymal stem cell,etc;MSC is widely used in the current skin treatment.With the development of tissue engineering,more and more cell factors,biomaterials and cytokines,biomaterials combined of stem cells apply in wound healing,but the results of the present study still cannot meet the clinical needs of different patients,not to solve the problem of skin appendage regeneration and exogenous related treatment signal mechanism.Our research group recently used a thermosensitive hydrogel modified by PAAs to combine with BMSCs in the treatment of chronic ulcers.We found that this kind of hydrogel could inhibit inflammation,regulate BMSCs to secrete cytokines and promote wound healing.But this kind of hydrogel degradation was relatively slow in vivo,so in this paper,on the basis of the above research,we modified synthetic material PAAs hydrogel and improved the degradation efficiency to achieve a better therapeutic effect on expectations.Secondly,although the use of BMSCs as seed cells have a good therapeutic effect,not all skin injury patients can be treated by using BMSCs,for example,the patients who are suffering from blood diseases or bone marrow dilution after multiple extraction of bone marrow.In recent years,another kind of mesenchymal stem cells-adipose derived mesenchymal stem cells(ADSCs)with its simple separation,rich source,has attracted much attention,which is a good kind of seed cells in tissue engineering.Combined with our previous study found that the cytokine Activin B promote re-epithelialization of skin and regeneration of hair follicle,aiming at the problems in the treatment of wound healing efficacy,this study explored the effect of Activin B combined with ADSCs in the treatment of skin wound and its signal mechanism,and provide basis for the study on the application of ADSCs as seed cells in skin tissue engineering,but also for our final construction of tissue engineering skin research1.BMSCs combined with new thermosensitive hydrogel can accelerate skin wound healing by promoting growth factor secretion(1)Background and PurposeBMSCs has the potential of multi-directional differentiation,it also can easily to be drawn,cultured in vitro,and low immunogenicity characteristics.Thermosensitive hydrogel,its physical properties and good biological compatibility,create a relatively stable environment for aseptic wound,and also create favorable conditions for cell transplantation,based on the previous research,used of new chemical functional groups to synthesis and modify PAAs crosslinking agent,improved the degradation rate of hydrogel in vitro,regulated cell biological events,and the hydrogel called HB-PAAs-thermosensitive hydrogel,and investigated the therapeutic applications of BMSCs combined with HB-PAAs-hydrogel on the skin healing.(2)ObjectiveCombined HB-PAAs-thermosensitive hydrogel with BMSCs to clarify the therapeutic function and effect of this new thermosensitive hydrogel(3)Methods and resultsFirst,prepared the new thermosensitive hydrogel and detected the swelling,degradation rate and cell toxicity,the results showed that the cell toxicity of HB-PAAs-thermosensitive hydrogel had a faster degradation rate and lower cytotoxicity.Primary isolated and cultured BMSCs,making skin trauma model in mice,used HB-PAAs-thermosensitive hydrogel BMSCs wrapped to deal with the skin wounds,and by the morphological observation we found that hydrogel combined with BMSCs significantly improve the wound healing rate and healing quality.Further study found that hydrogel could promote wound tissue to secrete TGF-?1 and bFGF,hydrogel combined with BMSCs could significantly promote the wound and the flange epithelial cell proliferation,reduce wound inflammation,regulated the deposition of collagen.(4)ConclusionHydrogel combined with BMSCs can promote the healing of skin wound by promoting the secretion of growth factors2.Activin B regulates ADSCs mediated wound healing through the MAPK signaling pathway(1)backgroundADSCs is a kind of multipotent stromal cells and has rich source,which regarded as the alternative seed cells,the skin wound healing in the treatment effect and the signal mechanism are not entirely clear.Activin B is a member of the TGF-superfamily,it has an important role in regulating the normal function of epithelial cells,skin development and wound healing,combined with our previous research foundation,this study investigated the efficacy of Activin B combined with ADSCs in the treatment of skin wound and its signal mechanism.(2)ObjectiveTo investigate the effect of ActivinB combined with ADSCs in skin wound healing and its signal mechanism(3)Methods and esultsTo explore by cell scratch,Transwell and phalloidine immunostaining experiments in vitro,we found that ActivinB regulates the generation and distribution of ADSCs actin stress fibers,and promote their migration.Based on the construction of mouse wound model,ActivinB combined with ADSCs,the results showed that ActivinB combined with ADSCs could promote wound contraction,promote the proliferation of epidermal cells,regulated collagen deposition and angiogenesis,,and accelerated wound healing.Further study found that ActivinB regulates the generation and distribution of ADSCs actin stress fibers through the MAPK signaling pathway,which induced cell migration and accelerated wound healing(4)ConclusionActivinB regulates the generation and distribution of ADSCs actin stress fibers through the MAPK signaling pathway,which promoted cell migration and accelerated wound healing...
Keywords/Search Tags:skin wound healing, bone marrow mesenchymal stem cells, adipose derived mesenchymal stem cells, hydrogel, Activin B
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