An overview of current advancements in pancreatic islet transplantation into the omentum

Damyar, Kimia; Farahmand, Vesta; Whaley, David; Alexander, Michael P.; Lakey, Jonathan R. T.

doi:10.1080/19382014.2021.1954459

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…An alternative to transplantation is to implant a renewable source of insulin-producing cells [11]. In the initial trials and early stages of clinical trials, pancreatic islet transplants require repeated use of immunosuppressive drugs [12]. The use of these drugs predisposes the patient to a variety of diseases, especially infectious diseases [13].…”

Section: Research Articlementioning

confidence: 99%

Insulin-producing cells from bone marrow stem cells versus injectable insulin for the treatment of rats with type I diabetes

Azeez

Jafar

Aziziaram³

et al. 2021

Cell. Mol. Biomed. Rep.

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Recently, stem cells have been considered renewable cell sources in the treatment of diabetes and the development of insulin-producing cells. In this regard, the current study aimed to compare Insulin-producing cells from bone marrow stem cells with injectable insulin in rats with type I diabetes. For this purpose, 40 rats were divided into four groups: the control or healthy group, the diabetic control group, the group that received differentiated insulin-producing cells from bone marrow, and the group that received insulin treatment. To differentiate insulinproducing cells from bone marrow, the femoral bone marrow of rats was extracted using the flushing method. Differentiated cells were evaluated using dithizone-specific dye, anti-insulin-proinsulin antibodies, and antiinsulin beta receptors. Also, the expression of the pdx-I gene, as the specific gene of pancreatic cells, was examined by RT-PCR. The results showed that transplantation of insulin-producing cells could significantly increase blood insulin levels in diabetic rats. This increase intensified in the second stage of transplantation when more cells were injected into rats. Concerning decreasing blood sugar levels, differentiated cells were able to reduce blood sugar levels significantly. Even in the first stage of cell injection, in which the rats received a small number of cells, their blood sugar levels were controlled by these cells. As a result, the present study showed that repeated transplants of insulin-producing cells differentiated from bone marrow could decrease blood sugar and increase insulin levels. Article info

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Section: Research Articlementioning

confidence: 99%

Insulin-producing cells from bone marrow stem cells versus injectable insulin for the treatment of rats with type I diabetes

Azeez

Jafar

Aziziaram³

et al. 2021

Cell. Mol. Biomed. Rep.

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“…Among the alternatives, the greater omentum has shown promise, both experimentally [ 2 , 23 ] and in human pilot trials [ 24 , 25 ]. The advantages of the omentum include its high vascularization, its easy surgical accessibility, and its large surface area, which allows transplantation of larger and less purified or encapsulated islet grafts and the possibility of graft retrieval, when needed [ 31 ]. However, the most important advantage is that transplantation into the omentum eliminates the risk of direct contact with the recipient’s blood.…”

Section: Discussionmentioning

confidence: 99%

Decellularized Pancreatic Tail as Matrix for Pancreatic Islet Transplantation into the Greater Omentum in Rats

Berková

Zacharovová

Patikova

et al. 2022

JFB

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Infusing pancreatic islets into the portal vein currently represents the preferred approach for islet transplantation, despite considerable loss of islet mass almost immediately after implantation. Therefore, approaches that obviate direct intravascular placement are urgently needed. A promising candidate for extrahepatic placement is the omentum. We aimed to develop an extracellular matrix skeleton from the native pancreas that could provide a microenvironment for islet survival in an omental flap. To that end, we compared different decellularization approaches, including perfusion through the pancreatic duct, gastric artery, portal vein, and a novel method through the splenic vein. Decellularized skeletons were compared for size, residual DNA content, protein composition, histology, electron microscopy, and MR imaging after repopulation with isolated islets. Compared to the other approaches, pancreatic perfusion via the splenic vein provided smaller extracellular matrix skeletons, which facilitated transplantation into the omentum, without compromising other requirements, such as the complete depletion of cellular components and the preservation of pancreatic extracellular proteins. Repeated MR imaging of iron-oxide-labeled pancreatic islets showed that islets maintained their position in vivo for 49 days. Advanced environmental scanning electron microscopy demonstrated that islets remained integrated with the pancreatic skeleton. This novel approach represents a proof-of-concept for long-term transplantation experiments.

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“…41 Additionally, further investigations have shown that the required islet mass to achieve euglycemia is lower in omentum sites compared to intrahepatic locations. 42 In addition to use of optimal transplantation sites, encapsulation methods can also increase cell viability and survival rates. 8 Encapsulation provides a support structure for the islets that mimics the native pancreatic extracellular matrix (ECM) and a physical barrier that prevents graft rejection and innate inflammatory responses.…”

Section: Identifying Clinical Outcomesmentioning

confidence: 99%

“…Hawthorne et al demonstrated that a pancreas graft in the renal capsule in a porcine model showed resistance to hypoxic‐related injury and a shorter recovery time to graft function 41 . Additionally, further investigations have shown that the required islet mass to achieve euglycemia is lower in omentum sites compared to intrahepatic locations 42 …”

Section: Building a Target Product Profile For Ictmentioning

confidence: 99%

Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile

Brauns

Sluder

et al. 2023

FASEB BioAdvances

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While progress has been made in the development of islet cell transplantation (ICT) as a viable alternative to the use of exogenous insulin therapy in the treatment of type 1 diabetes, it has not yet achieved its full potential in clinical studies. Ideally, ICT would enable lifelong maintenance of euglycemia without the need for exogenous insulin, blood glucose monitoring or systemic immune suppression. To achieve such an optimal result, therapeutic approaches should simultaneously promote long‐term islet viability, functionality, and localized immune protection. In practice, however, these factors are typically tackled individually. Furthermore, while the requirements of optimal ICT are implicitly acknowledged across numerous publications, the literature contains few comprehensive articulations of the target product profile (TPP) for an optimal ICT product, including key characteristics of safety and efficacy. This review aims to provide a novel TPP for ICT and presents promising tried and untried combinatorial approaches that could be used to achieve the target product profile. We also highlight regulatory barriers to the development and adoption of ICT, particularly in the United States, where ICT is only approved for use in academic clinical trials and is not reimbursed by insurance carriers. Overall, this review argues that the clear definition of a TPP in addition to the use of combinatorial approaches could help to overcome the clinical barriers to the widespread adoption of ICT for the treatment of type 1 diabetes.

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An overview of current advancements in pancreatic islet transplantation into the omentum

Cited by 19 publications

References 29 publications

Insulin-producing cells from bone marrow stem cells versus injectable insulin for the treatment of rats with type I diabetes

Insulin-producing cells from bone marrow stem cells versus injectable insulin for the treatment of rats with type I diabetes

Decellularized Pancreatic Tail as Matrix for Pancreatic Islet Transplantation into the Greater Omentum in Rats

Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile

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