The Influence of Microenvironment on Survival of Intraportal Transplanted Islets

Yan, Lingling; Ye, Liping; Chen, Yahong; He, Sai-qin; Zhang, Chenyang; Mao, Xin-Li; Li, Shaowei

doi:10.3389/fimmu.2022.849580

Cited by 7 publications

(6 citation statements)

References 137 publications

(161 reference statements)

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“…When isolated islets are exposed to blood, the complement system is quickly activated, leading to the lysis of islet cells. At the same time, the production of the allergic toxins C3a and C5a further induces the aggregation of macrophages and neutrophils and promotes mononuclear cells to release cytokines such as IL-1, IL-6, IL-8, and TNF-α ( 50 ).…”

Section: Activation and Role Of Macrophages In The Ibmirmentioning

confidence: 99%

“…After activation, they produce various chemokines to attract mononuclear cells and macrophages; in addition, the infiltration of neutrophils leads to the release of cytokines from T cells and macrophages, such as tumor necrosis factor α (TNF-α) and macrophage inflammatory protein 1α. The mobilization of this immune effector could not only expand IBMIR but also induce subsequent adaptive immunity, inducing and enhancing cellular rejection responses ( 50 , 51 ) ( Figure 1 ).…”

Section: Activation and Role Of Macrophages In The Ibmirmentioning

confidence: 99%

“…T cells also express Fas receptor-associated ligands and TNF-related apoptosis-inducing ligands, activating effector caspases to cause cellular apoptosis. In addition, CD8+ T cells directly contact and promote the release of granzyme B into the cytoplasm of target cells through perforin, thereby activating nucleases and caspases to kill target cells ( 11 , 50 , 53 ).…”

Section: Activation and Role Of Macrophages In The Ibmirmentioning

confidence: 99%

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Advancements in innate immune regulation strategies in islet transplantation

Duan,

Liu,

Zhang

et al. 2024

Front. Immunol.

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As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research.

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Section: Activation and Role Of Macrophages In The Ibmirmentioning

confidence: 99%

Section: Activation and Role Of Macrophages In The Ibmirmentioning

confidence: 99%

Section: Activation and Role Of Macrophages In The Ibmirmentioning

confidence: 99%

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Advancements in innate immune regulation strategies in islet transplantation

Duan,

Liu,

Zhang

et al. 2024

Front. Immunol.

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“… 27 Hypoxia has been shown to decrease insulin secretion and to induce several forms of cell death, from necrosis to apoptosis. 28 , 29 …”

Section: Introductionmentioning

confidence: 99%

3D evaluation of the extracellular matrix of hypoxic pancreatic islets using light sheet fluorescence microscopy

Ramirez,

Bastien,

Chae

et al. 2024

Islets

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Pancreatic islet transplantation is a promising treatment for type 1 diabetes, but the survival and function of transplanted islets are hindered by the loss of extracellular matrix (ECM) during islet isolation and by low oxygenation upon implantation. This study aimed to evaluate the impact of hypoxia on ECM using a cutting-edge imaging approach based on tissue clearing and 3D microscopy. Human and rat islets were cultured under normoxic (O 2 21%) or hypoxic (O 2 1%) conditions. Immunofluorescence staining targeting insulin, glucagon, CA9 (a hypoxia marker), ECM proteins (collagen 4, fibronectin, laminin), and E-cadherin (intercellular adhesion protein) was performed on fixed whole islets. The cleared islets were imaged using Light Sheet Fluorescence Microscopy (LSFM) and digitally analyzed. The volumetric analysis of target proteins did not show significant differences in abundance between the experimental groups. However, 3D projections revealed distinct morphological features that differentiated normoxic and hypoxic islets. Under normoxic conditions, ECM could be found throughout the islets. Hypoxic islets exhibited areas of scattered nuclei and central clusters of ECM proteins, indicating central necrosis. E-cadherin was absent in these areas. Our results, demonstrating a diminution of islets’ functional mass in hypoxia, align with the functional decline observed in transplanted islets experiencing low oxygenation after grafting. This study provides a methodology combining tissue clearing, multiplex immunofluorescence, Light Sheet Fluorescence Microscopy, and digital image analysis to investigate pancreatic islet morphology. This 3D approach allowed us to highlight ECM organizational changes during hypoxia from a morphological perspective.

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“…Islet cell transplantation can induce a rapid inflammatory reaction in the circulation, leading to the loss of the vast majority of transplanted islets. The use of large doses of immunosuppressants during transplantation compromises the long-term viability and function of the graft, and the need for long-term immunosuppressive medications after the transplant poses a risk of organ damage, malignancies, new infections, and new-onset T1D in patients [ 12 ]. The high cost of islet transplantation and the paucity of human cadaveric islets highlight the urgent need for innovative pancreatic islet transplantation procedures [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes

Jayasinghe¹,

Prathiraja²,

Perera³

et al. 2022

Cureus

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Type 1 diabetes (T1D) is a chronic disease characterized by inadequate or absent insulin production due to the autoimmune destruction of beta (β) cells in the pancreas. It was once called "juvenile diabetes" since the disease frequently occurs in children, but it can also develop in adults. According to the International Diabetes Federation, an estimated 700 million adults will suffer from diabetes by 2045. Although the exact cause of diabetes remains unknown, it is hypothesized that genetic factors, environmental factors, and exposure to certain viruses play a role in the development of T1D. To date, exogenous insulin is the most common treatment for T1D. However, it is not a cure for the disease. Islet cell transplantation and pancreatic transplantation are two additional treatments that have gained popularity in recent years, but their clinical application may be limited by the need for high doses of immunosuppressants, the rarity of human cadaveric islets, and the need for extensive surgery in pancreatic transplantation. Mesenchymal stem cells (MSCs) are a highly promising novel treatment for T1D and their discovery has advanced biological sciences by allowing for modification of cell fate and the development of higher-order cellular structures. They play an essential role in lowering levels of fasting blood sugar, hemoglobin A1c, and C-peptide, and in treating microvascular complications associated with T1D. However, some of the disadvantages of its use in clinical practice are limited to its method of collection, proliferation rate, cell activity with age, and the risk of tumour formation identified in some studies. Large-scale studies are required to discover the mechanism of action of MSCs after administration as well as the optimal route, dose, and timing to maximize the benefits to patients. This article focuses primarily on the role of MSCs in the treatment of T1D and compares the feasibility, benefits, and drawbacks of MSCs in the treatment of T1D.

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The Influence of Microenvironment on Survival of Intraportal Transplanted Islets

Cited by 7 publications

References 137 publications

Advancements in innate immune regulation strategies in islet transplantation

Advancements in innate immune regulation strategies in islet transplantation

3D evaluation of the extracellular matrix of hypoxic pancreatic islets using light sheet fluorescence microscopy

The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes

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