A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

Goddard, Erica T.; Fischer, Jacob; Schedin, Pepper

doi:10.3791/54903-v

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Based on the study by Erica T. Goddard et al, 20 male rats were treated with 100 µL of 0.015 mg/mL buprenorphine subcutaneously, 1 h before surgery for pain management. The rats were anesthetized 2%–2.5% isoflurane in oxygen.…”

Section: Methodsmentioning

confidence: 99%

Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose‐sensitive promoter in the port vein

Mohammad Dezashibi,

Farzad‐Mohajeri,

Bandehpour

et al. 2023

Cell Biochemistry & Function

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The treatment of type 1 diabetes through islet cell transplantation is a complex process, facing challenges such as allograft rejections and a limited supply of donors. One potential solution is to utilize the liver as an alternative for natural insulin production, as hepatocytes can secrete proteins and respond to glucose levels. Recent research has shown promising results in using mesenchymal stem cells as a potential cure for diabetes. The study utilized a diabetic rat model, confirmed through blood sugar measurement. A plasmid vector was designed with specific genetic components, synthesized by biotech company, and then Inserted vector into a plasmid with resistance genes and bacterial origin. Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) were cultured and transfected with the plasmid using Lipofectamine 3000. Polymerase chain reaction was employed to confirm successful transfection using specific primers. For the animal study, 30 male Wistar rats were divided into six groups, each comprising five rats. The control group did not receive any treatment, while the second group received MSCs via Portal Vein Injection. The third group received MSCs transfected with a specific construct via Portal Vein Injection. The fourth group was induced to develop diabetes through streptozotocin (STZ) injection, the fifth group developed diabetes and received untransfected MSCs via Portal Vein Injection, and the sixth group received MSCs transfected with the specific construct via Portal Vein Injection. To manage Pain, appropriate pain control was administered to the rats for 3 days after the surgery. Fixed liver tissues obtained from the euthanized rats were utilized for immunohistochemistry. In this study, immunohistochemical techniques were used to examine insulin expression in different groups of rats. The control groups showed high levels of insulin expression, while the diabetic groups exhibited lower expression. However, there was a significant difference between the diabetic groups treated with MSC and transgenic MSC cells. All groups had similar baseline glucose levels, but the diabetic groups showed a significant increase after STZ injection, whereas the control and MSC groups did not. Postintervention, both the control and MSC groups had similar glucose levels to the post‐STZ levels. However, diabetes‐induced groups experienced a significant decrease in glucose levels, with the transfected MSCs showing a greater decrease than the untransfected MSCs. The study suggested that treatment with MSCs, especially transfected ones, can effectively reduce glucose levels in rats with diabetes. In this research, rat BM‐MSCs were utilized to create insulin‐producing mesenchymal cells with glucose‐sensitive insulin expression. The cells were transferred to the liver of diabetic rats via portal vein injection, leading to an increase in insulin expression. This study proposes a novel approach for cell therapy and delivery in the treatment of type 1 diabetes.

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Section: Methodsmentioning

confidence: 99%

Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose‐sensitive promoter in the port vein

Mohammad Dezashibi,

Farzad‐Mohajeri,

Bandehpour

et al. 2023

Cell Biochemistry & Function

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“…To study islet transplantation outcomes in humans, preclinical studies in mice are used to test new potential treatments. Currently, preclinical studies are performed using an open laparotomy procedure, 14 whereby the abdomen of the mouse is opened via a midline incision, the hepatic portal vein (HPV) is located through the temporary relocation of the intestines, and the injection is administered 14,15 . Although this is a well established preclinical procedure, it does not emulate the procedure used in the clinical setting, where injection into the HPV is done using laparoscopic‐guidance 10 …”

Section: Introductionmentioning

confidence: 99%

“…Currently, preclinical studies are performed using an open laparotomy procedure, 14 whereby the abdomen of the mouse is opened via a midline incision, the hepatic portal vein (HPV) is located through the temporary relocation of the intestines, and the injection is administered. 14,15 Although this is a well established preclinical procedure, it does not emulate the procedure used in the clinical setting, where injection into the HPV is done using laparoscopic-guidance. 10 Preclinical ultrasound-guided HPV injections are associated with a diminished risk of bleeding, infection and shorter recovery times versus an open laparotomy technique.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‐guided hepatic portal vein injection is not a reproducible technique for delivery of cell therapies to the liver in mice

et al. 2023

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BackgroundOpen laparotomy hepatic portal vein injection is a well‐used pre‐clinical technique for transplantation of cell therapies to the liver in mice, including islet transplantation studies for type 1 diabetes. We hypothesised that ultrasound‐guided hepatic portal vein injection in mice would provide reproducible and reliable results, as is currently obtained via open laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans.MethodsFluorescent‐polymer microparticles (20 μm) were injected (27G‐needle) into the hepatic portal vein via open laparotomy (n=4) or under ultrasound‐guidance (n=4) using an MX550D‐transducer with a Vevo3100‐scanner (FUJIFILM VisualSonics, Inc., Canada). Mice were culled 24‐hours post injection; organs were frozen, step sectioned (10 μm‐slices,) and 10 sections/mouse (50 μm‐spacing) were quantified for microparticles in the liver and other organs by fluorescent microscopy.ResultsMurine hepatic portal vein injection, via open laparotomy‐route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasound‐guided injection resulted in reduced microparticle delivery (p<0.0001) and microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median(IQR) 4.15(0.00‐4.15) versus 0.00(0.00‐0.00) particle‐count mm‐2, respectively.ConclusionsUltrasound‐guided injection results in microparticle clustering in the liver, with an overall reduction in microparticle number when compared to open laparotomy hepatic portal vein injection, and high variability in microparticle‐counts detected between mice. Ultrasound‐guided injection is not currently a technique that can replace open laparotomy hepatic portal vein injection of islet transplantation in mice.

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State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?

Nuckhir,

Withey,

Cabral

et al. 2024

J Mammary Gland Biol Neoplasia

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Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis.

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A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

Cited by 5 publications

References 43 publications

Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose‐sensitive promoter in the port vein

Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose‐sensitive promoter in the port vein

Ultrasound‐guided hepatic portal vein injection is not a reproducible technique for delivery of cell therapies to the liver in mice

State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?

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