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Establishing A Decellularized Tumor-bearing Rabbit Liver Model Mediated By Liver Decellularized Matrix In Regenerative Medicine

Posted on:2021-02-26Degree:MasterType:Thesis
Country:ChinaCandidate:J B XuFull Text:PDF
GTID:2404330605958210Subject:Imaging and nuclear medicine
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BackgroundPrimary liver cancer is a relatively common malignant tumor in China,with a high incidence.Liver cancer has the characteristics of easy recurrence and intrahepatic metastasis.Most patients have lost the opportunity for surgical resection at the time of diagnosis.Although the main treatment of liver cancer in the middle and late stage has reached a consensus,it is repeated TACE.However,most of the quantitative indicators during the operation are still based on clinical experience and retrospective research,and lack of basic research basis.In addition,the current research on the spatial distribution of drug-loaded microspheres during TACE surgery is basically limited to the bionic blood vessel model and cannot replicate the geometric characteristics of the vascular system.The preparation of a complete decellularized liver matrix(DLM)by decellularization is a cutting-edge technology in the field of regenerative tissue engineering.DLM is a temporary physical support used in combination with functional cells to prepare tissue/organ constructs.The decellularized scaffold has the natural structure of the entire organ design at the micro and nano structure levels,with the advantages of visibility and retention of the native blood vessel architectureAt present,the decellularized liver matrix has been relatively mature in the field of regenerative medicine,and the VX2 tumor-bearing rabbit liver model has gradually become popular in interventional research experiments.The concept of a decellularized VX2 tumor-bearing rabbit liver model combining the two is still in the exploration stage.For interventional physicians,the decellularized VX2 tumor-bearing rabbit liver model can provide another new platform and new approach for basic interventional research.Objectives1.To explore the imaging performance of VX2 tumor-bearing rabbit liver and the optimal modeling time for tumor-bearing rabbit liver models?2.Assess whether it is possible to completely decellularize tumors in rabbit liver?3.To determine whether rabbit liver is suitable for the preparation of interventional acellular model.Can the vasculature after decellularization be subjected to DSA angiography,and the diameter of the targeted blood vessel that can be superselected?Materials and methodsNew Zealand white rabbits of 2—2.5 kg were purchased from the Experimental Animal Center of Southern Medical University.Hip tumor implantation,passage of rabbit liver tumors and dissection of livers were used to prepare normal rabbit liver and rabbit hepatocellular carcinoma acellular models,respectively.At the same time,ultrasound and magnetic resonance examinations were performed on VX2 tumor-bearing rabbit liver before decellularization.The optimal modeling time of tumor-bearing rabbit liver models was analyzed by judging the degree of tumor necrosis.Single liver lobes of rabbit liver and whole liver of rabbit VX2 tumors were decellularized in turn.The decellularization level of liver parenchyma and tumors is continuously evaluated during decellularization washing process.Verify that the decellularized rabbit liver model can perform DSA angiography,and measure the diameter of the target vessel that the model can over-select.ResultsWhen the rabbit liver VX2 tumor grew to 10 days,it showed an oval solid solid slightly higher echo group under ultrasound,showing a strong echogenic envelope,the echo in the mass was not uniform,and the echo-free area was visible.The color Doppler flow phenomenon(CDFI)shows that a wrap-around color blood flow signal can be seen around the mass.Both T2W and DWI showed a round-like high-signal shadow,the internal signal was not uniform,a few low-signal areas were visible,the boundaries were clear,and the edges were smooth.This indicates that the blood supply around the tumor is abundant,and there is a little necrosis in the central part due to lack of blood supply.The second week after tumor implantation is the best time to establish a tumor model,although there will be some necrosis due to lack of blood supply in the tumor center,the tumor volume is moderate.The total duration of complete decellularization of single liver lobe and whole liver of normal rabbit liver was 16 hours and 48 hours.The vascular network system of decellularized VX2 tumor-bearing rabbit liver model is complete,and it is a visual model for the naked eye.Although we performed a 48-hour decellularization wash on VX2 tumor-bearing rabbit liver model,the tumors could not be completely decellularized.The DSA angiography of decellularized rabbit liver matrix showed that the furthest vascular in the liver that can be selected is the branch of grade 3,that is,the main branch of the vein in the liver lobe.ConclusionsThe growth of VX2 tumors in living rabbit liver can be determined by ultrasound and magnetic resonance.The best time to establish a tumor model is 2 weeks after tumor implantation.The total time to achieve complete decellularization of the whole liver is 48 hours,which is three times that of decellularization of a single liver lobe.On the premise of maintaining the rigidity of the extracellular matrix of the whole liver,further research is needed to achieve complete decellularization of VX2 tumors.This issue cannot be coordinated effectively at this time.The target vessel that the microcatheter can superselect in the decellularized rabbit liver matrix is a grade 3 branch,that is,the main branch of the vein of the liver lobe.The application of decellularized VX2 tumor-bearing rabbit liver model in the field of interventional therapy has guiding significance.
Keywords/Search Tags:Liver tumor, Rabbit, VX2, Animal model, Decellularization, Blood vessel
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