MaltSci 麦伴科研

Appearance

Popular Reports / transplantation

This report is written by MaltSci based on the latest literature and research findings

How does islet cell transplantation treat diabetes? ​

Abstract ​

Diabetes mellitus, particularly type 1 diabetes (T1D), is a chronic metabolic disorder characterized by the autoimmune destruction of insulin-producing beta cells in the pancreas. This condition significantly impacts millions globally, necessitating innovative therapeutic approaches beyond traditional insulin therapy. Islet cell transplantation has emerged as a viable option, involving the isolation of islet cells from donor pancreases and their transplantation into the recipient's liver to restore insulin production. This review explores the mechanisms by which islet cell transplantation alleviates diabetes, evaluates current clinical practices, and discusses recent advancements and future directions. Key findings indicate that islet transplantation can achieve near-normal glycemic control, reduce or eliminate the need for exogenous insulin, and mitigate diabetes-related complications. However, challenges such as donor organ shortages, the need for lifelong immunosuppression, and the risk of islet cell loss post-transplantation remain significant hurdles. Recent studies have shown promising short-term outcomes, yet long-term graft survival is a concern, with many recipients regaining insulin dependence within a few years. Innovative approaches, including the co-transplantation of mesenchymal stem cells and hydrogel encapsulation techniques, are being explored to enhance islet function and survival. This review aims to provide comprehensive insights into the efficacy and limitations of islet transplantation, contributing to the ongoing discourse surrounding diabetes management strategies.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 Overview of Diabetes and Its Treatment
    • 2.1 Pathophysiology of Diabetes
    • 2.2 Current Treatment Modalities
  • 3 Islet Cell Transplantation: An Overview
    • 3.1 Definition and Process of Islet Cell Transplantation
    • 3.2 Indications for Islet Cell Transplantation
  • 4 Mechanisms of Action
    • 4.1 Restoration of Insulin Secretion
    • 4.2 Immune Modulation and Tolerance
  • 5 Clinical Outcomes and Challenges
    • 5.1 Success Rates and Long-term Outcomes
    • 5.2 Complications and Limitations
  • 6 Recent Advances and Future Directions
    • 6.1 Innovations in Islet Preservation
    • 6.2 Emerging Techniques in Transplantation
  • 7 Conclusion

1 Introduction ​

Diabetes mellitus, particularly type 1 diabetes (T1D), is a chronic metabolic disorder characterized by the autoimmune destruction of insulin-producing beta cells in the pancreas. This condition affects millions globally, imposing significant health burdens and economic costs. Current management strategies primarily involve lifelong insulin therapy and glucose monitoring, which, while effective in maintaining glycemic control, do not address the underlying deficiency of insulin production and can lead to severe complications, including hypoglycemia and long-term vascular damage [1]. As such, there is an urgent need for innovative therapeutic approaches that can restore endogenous insulin secretion and improve the quality of life for patients.

Islet cell transplantation has emerged as a viable treatment option for individuals with T1D and certain cases of type 2 diabetes (T2D). This procedure involves the isolation of islet cells from donor pancreases and their transplantation into the recipient's liver, where they can potentially restore normal insulin production [2]. The significance of this intervention lies in its ability to achieve near-normal glycemic control, reduce or eliminate the need for exogenous insulin, and mitigate the risk of diabetes-related complications [3]. However, despite its potential benefits, islet transplantation faces several challenges, including a shortage of suitable donor organs, the necessity for lifelong immunosuppression to prevent graft rejection, and the risk of islet cell loss post-transplantation [4].

Recent advancements in islet transplantation have highlighted both the efficacy and limitations of this therapeutic strategy. For instance, studies have shown that while the short-term outcomes of islet transplantation are promising, long-term graft survival remains a significant concern, with many recipients regaining insulin dependence within a few years [5]. Factors contributing to this decline include immune-mediated rejection, islet cell dysfunction, and the effects of chronic inflammation [3]. Moreover, emerging research has explored innovative approaches to enhance islet transplantation outcomes, such as the co-transplantation of mesenchymal stem cells to improve islet function and survival [6], as well as the use of hydrogel encapsulation techniques to protect islet cells from immune attacks [7].

This review will comprehensively explore the mechanisms by which islet cell transplantation alleviates diabetes, evaluate the current state of clinical practices, and discuss recent advancements and future directions in the field. The report is organized as follows: Section 2 provides an overview of diabetes and its treatment modalities, including the pathophysiology of diabetes and existing therapeutic options. Section 3 presents a detailed overview of islet cell transplantation, including its definition, process, and indications. Section 4 delves into the mechanisms of action, focusing on the restoration of insulin secretion and the role of immune modulation. Section 5 examines clinical outcomes and challenges, highlighting success rates, long-term outcomes, and potential complications. Finally, Section 6 discusses recent advances and future directions, including innovations in islet preservation and emerging transplantation techniques. Through this structured examination, we aim to contribute valuable insights into the efficacy and limitations of islet transplantation, thereby enhancing the ongoing discourse surrounding diabetes management strategies.

2 Overview of Diabetes and Its Treatment ​

2.1 Pathophysiology of Diabetes ​

Islet cell transplantation serves as a therapeutic strategy for treating diabetes, particularly type 1 diabetes, by addressing the underlying issue of insulin deficiency. In diabetes, especially type 1, the body's immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas, leading to insufficient insulin production and the resultant hyperglycemia. This condition necessitates continuous management, often through insulin therapy, which can be complicated by the risk of severe hypoglycemia and other long-term complications, including retinopathy, nephropathy, and cardiovascular disease[8][9].

Islet transplantation involves isolating islets from a donor pancreas and transplanting them into a recipient, where they can restore endogenous insulin production. This procedure has shown promise in significantly improving glycemic control and reducing the incidence of hypoglycemic episodes. Notably, it allows patients to achieve a normoglycemic state without the burdens of daily insulin injections[9][10]. However, the widespread application of islet transplantation is hampered by several challenges, including a severe shortage of donor organs, the need for immunosuppressive therapy to prevent graft rejection, and complications arising from such therapies[4][7].

Recent advancements have focused on overcoming these barriers. Strategies include the development of hydrogel-encapsulated islet cells, which aim to provide immunoisolation, thereby reducing the need for immunosuppressive drugs and improving transplant outcomes[7]. Additionally, research into alternative sources of islet cells, such as stem cells, is underway, which could potentially offer an unlimited supply of insulin-producing cells and mitigate the challenges associated with donor organ scarcity[11][12].

Moreover, clinical trials, such as the Edmonton Protocol, have introduced glucocorticoid-free immunosuppressive regimens, which have demonstrated improved outcomes in terms of islet function and patient insulin independence[2][13]. Despite these advancements, islet transplantation remains an experimental and resource-intensive procedure, and further research is essential to refine techniques and enhance the viability and availability of islet cells for transplantation[8][9].

In summary, islet cell transplantation offers a potentially curative approach for type 1 diabetes by replenishing the lost beta cells and restoring normal insulin production. Continued research and innovation in this field are crucial to addressing the current limitations and improving the long-term success of islet transplantation as a standard treatment modality for diabetes.

2.2 Current Treatment Modalities ​

Islet cell transplantation is an emerging therapeutic option for the treatment of diabetes, particularly type 1 diabetes mellitus. This procedure involves the isolation of islets of Langerhans from donor pancreases and their subsequent transplantation into a diabetic recipient. The primary aim of islet transplantation is to restore endogenous insulin production, thereby reducing or eliminating the need for exogenous insulin therapy.

The advantages of islet transplantation over traditional diabetes treatments include its minimally invasive nature and the ability to utilize islets from pancreases that may not be suitable for whole organ transplantation. Unlike pancreas transplants, which require major surgery and long-term immunosuppression, islet transplantation can be performed via intravenous infusion of islets into the portal vein, significantly reducing surgical risks [2].

Despite its potential, the widespread application of islet transplantation is limited by several challenges. One of the primary obstacles is the shortage of donor organs, which hampers the availability of islets for transplantation. Additionally, recipients often face issues related to immune rejection of the transplanted islets, necessitating the use of immunosuppressive therapies. These therapies can be toxic to the beta cells and may compromise the long-term function of the transplanted islets [4].

The clinical outcomes of islet transplantation have improved over the years, particularly following the introduction of new immunosuppressive protocols. For instance, the Edmonton Protocol demonstrated that a glucocorticoid-free immunosuppressive regimen could lead to long-term successful outcomes in islet transplantation. In recent studies, insulin independence rates post-transplantation have been reported to reach levels between 50% and 80% [10].

Moreover, advancements in islet preservation techniques and the exploration of alternative sources of islet cells, such as stem cells, are promising avenues for overcoming current limitations. Stem cell-derived insulin-producing cells have shown potential in preclinical models, suggesting a future where islet transplantation could become more widely available and less reliant on donor organ availability [11].

In conclusion, islet cell transplantation represents a significant advancement in the treatment of diabetes, offering a potential cure by restoring the body's ability to produce insulin. However, ongoing research is necessary to address the challenges of donor shortages, immune rejection, and the need for immunosuppressive therapy to enhance the success rates and accessibility of this treatment modality [3][7].

3 Islet Cell Transplantation: An Overview ​

3.1 Definition and Process of Islet Cell Transplantation ​

Islet cell transplantation is a medical procedure aimed at treating insulin-dependent diabetes mellitus, particularly type 1 diabetes. This process involves the transplantation of isolated islets of Langerhans, which are clusters of cells in the pancreas that produce insulin, from a donor pancreas into a recipient. The primary goal of this transplantation is to restore the recipient's ability to produce insulin, thereby improving glycemic control and reducing or eliminating the need for exogenous insulin injections.

The process of islet cell transplantation typically includes several key steps. Initially, islets are isolated from a donor pancreas through a meticulous procedure that separates the islets from the surrounding pancreatic tissue. Following isolation, the islets are purified and assessed for viability before being transplanted into the recipient. This transplantation can be performed via an intravenous infusion, usually into the portal vein, which directs the islets to the liver, where they can function similarly to their natural environment in the pancreas.

Despite its potential, islet transplantation faces several challenges. One of the most significant obstacles is the loss of islet cells before and after transplantation due to factors such as oxidative stress, immune rejection, and the surgical process itself. It has been observed that many recipients experience a decline in islet function over time, with a substantial percentage requiring insulin therapy again within a few years post-transplantation (Potter et al., 2014; Jamiolkowski et al., 2012). This loss of function can be attributed to mechanisms similar to those seen in type 2 diabetes, including inflammation and oxidative stress, indicating a need for improved protective strategies for the transplanted islets.

Recent advancements in the field have focused on enhancing islet survival and function. For instance, the co-transplantation of mesenchymal stem cells (MSCs) alongside islets has shown promise in improving graft survival due to MSCs' immunomodulatory properties and their ability to promote angiogenesis (Sakata et al., 2011). Additionally, innovations such as hydrogel encapsulation of islet cells are being explored to provide a protective environment that can mitigate immune responses and enhance islet function (Huan et al., 2024).

Furthermore, ongoing research is investigating alternative transplantation sites beyond the traditional portal vein approach, which may offer better outcomes in terms of graft survival and function. These include subcutaneous and intramuscular sites, which could provide a more favorable immunological environment for the transplanted islets (Cayabyab et al., 2021; Wang et al., 2024).

In conclusion, islet cell transplantation represents a significant therapeutic strategy for diabetes, particularly type 1 diabetes, by aiming to restore endogenous insulin production. While challenges remain regarding islet survival and function post-transplant, ongoing research and innovative techniques hold the potential to improve outcomes and expand the applicability of this treatment.

3.2 Indications for Islet Cell Transplantation ​

Islet cell transplantation serves as a promising treatment for diabetes, particularly type 1 diabetes mellitus, by providing a source of insulin-producing beta cells that can restore endogenous insulin production and improve glycemic control. The procedure involves isolating islets from a donor pancreas and infusing them into the recipient, allowing the transplanted islets to function and produce insulin in response to blood glucose levels.

The primary indication for islet cell transplantation is for patients with type 1 diabetes who experience severe hypoglycemia or have difficulty achieving stable glycemic control through conventional insulin therapy. The transplantation of islets has been shown to improve blood sugar levels and can significantly reduce or eliminate the incidence of hypoglycemia, which is a serious complication associated with insulin therapy (Cotterell & Kenyon, 2002) [8].

However, the widespread application of islet transplantation is limited by several factors, including a shortage of donor pancreases, the need for immunosuppressive therapy to prevent transplant rejection, and the complications associated with such therapies. Immunosuppressive drugs, while necessary to ensure the survival of transplanted islets, can have toxic effects and may pose additional health risks (Opara & Kendall, 2002) [9].

Recent advances in the field aim to address these challenges. For instance, the development of hydrogel-encapsulated islet cells is being explored as a strategy to enhance the success of islet transplantation. This technique involves encapsulating islet cells in a hydrogel matrix to provide immunoisolation, which may reduce the need for immunosuppressive drugs and improve transplant outcomes (Huan et al., 2024) [7]. Additionally, research into alternative sources of islet cells, such as stem cells, is ongoing, with the potential to provide an unlimited supply of insulin-producing cells for transplantation (Nakamura et al., 2021) [12].

Overall, islet cell transplantation represents a significant advancement in the treatment of diabetes, particularly for those who cannot achieve adequate control with insulin therapy alone. It offers the possibility of improved quality of life and a reduction in diabetes-related complications, although ongoing research is necessary to overcome the limitations currently faced in the field.

4 Mechanisms of Action ​

4.1 Restoration of Insulin Secretion ​

Islet cell transplantation is recognized as a potential curative approach for type 1 diabetes, primarily due to its ability to restore physiological insulin secretion. The mechanism of action underlying this treatment involves several key processes, including the reestablishment of coordinated pulsatile insulin secretion and the effective delivery of insulin to the hepatic circulation.

Intrahepatic islet transplantation specifically aims to address two critical questions regarding insulin secretion: whether transplanted islets can reestablish coordinated pulsatile insulin secretion in humans, and the extent to which this insulin is delivered to the hepatic sinusoids versus the hepatic central vein. Research has demonstrated that in islet transplant recipients, there is a restoration of coordinated pulsatile insulin secretion, which is crucial for maintaining glucose homeostasis. This is achieved through glucose-mediated stimulation of insulin secretion, which amplifies the insulin pulse mass. Studies involving direct catheterization of the hepatic vein have shown that approximately 80% of the insulin secreted by intrahepatic islets is extracted during the first pass, indicating that these islets effectively deliver insulin directly to the hepatic sinusoid, thereby restoring a portal mode of insulin delivery (Meier et al., 2006) [14].

Furthermore, the transplantation of pancreatic islets provides an opportunity to reintroduce a functional endocrine component into the diabetic patient's body. The transplantation process involves isolating islets from a donor pancreas and then transplanting them into the recipient's liver. Once in place, these islets begin to function similarly to endogenous islets, producing insulin in response to glucose levels. This process not only addresses the immediate need for insulin but also helps in the regulation of blood glucose levels, potentially alleviating the complications associated with diabetes.

However, it is important to note that the success of islet transplantation is often limited by factors such as the immune response against the transplanted tissue, which necessitates the use of immunosuppressive therapies. Despite advancements in immunosuppressive protocols that have improved islet survival rates, the long-term function of transplanted islets can decline over time, leading to a return to insulin dependence in many recipients (Potter et al., 2014) [5].

In conclusion, islet cell transplantation treats diabetes primarily by restoring the ability to secrete insulin in a coordinated manner in response to glucose, thereby improving glycemic control and potentially reversing some of the complications associated with diabetes. Continued research into improving islet viability, exploring new sources of insulin-producing cells, and enhancing immunosuppressive strategies is essential for optimizing outcomes in islet transplantation (Wang et al., 2024) [3].

4.2 Immune Modulation and Tolerance ​

Islet cell transplantation serves as a promising therapeutic approach for treating diabetes, particularly type 1 diabetes mellitus (T1D). The underlying mechanisms of action primarily revolve around immune modulation and the establishment of tolerance, which are critical for the success of the transplantation procedure.

Islet transplantation involves the transfer of isolated islets from a donor pancreas into a diabetic recipient, aiming to restore endogenous insulin production and improve glycemic control. However, a significant challenge in this therapeutic strategy is the immune response against the transplanted islets, necessitating the use of immunosuppressive therapies to prevent graft rejection. Chronic immunosuppression, while essential, poses risks such as increased susceptibility to infections and malignancies, highlighting the need for strategies that promote immune tolerance without long-term immunosuppression[15].

Recent advancements have focused on understanding the mechanisms of transplant immune tolerance. One promising approach is the induction of tolerance mediated by regulatory T cells (Tregs), particularly T regulatory type 1 (Tr1) cells, which are characterized by their production of interleukin-10 (IL-10). IL-10 plays a crucial role in modulating immune responses and promoting tolerance, thereby reducing the likelihood of rejection of the transplanted islets[16]. Studies have demonstrated that treatments combining IL-10 with agents like rapamycin can enhance the generation of Tr1 cells, leading to stable long-term tolerance in animal models[16].

Additionally, co-transplantation of mesenchymal stem cells (MSCs) alongside islets has shown potential in improving islet function and survival. MSCs exert immunomodulatory effects, promoting angiogenesis and protecting islets from immune-mediated damage. This strategy aims to create a more favorable environment for the transplanted islets, thus enhancing graft survival and function[6].

The exploration of encapsulation techniques represents another innovative strategy to achieve immune modulation. Encapsulated islets are shielded from the host immune system while retaining their ability to sense glucose and secrete insulin. This method minimizes the need for immunosuppressive therapy and addresses the challenge of immune rejection[9].

Moreover, the understanding of the immunological mechanisms underlying islet transplantation has led to the development of novel immunosuppressive protocols that are less toxic and more effective in promoting graft acceptance. For instance, the "Edmonton Protocol" introduced a steroid-free regimen that has significantly improved outcomes in islet transplantation, achieving higher rates of insulin independence among recipients[17].

In summary, the treatment of diabetes through islet cell transplantation hinges on effective immune modulation and the induction of tolerance. Ongoing research aims to refine these approaches, enhancing graft survival while minimizing the adverse effects associated with long-term immunosuppression. As advancements continue, the potential for islet transplantation to become a routine and effective treatment for diabetes grows, offering hope for improved quality of life for patients with this chronic condition.

5 Clinical Outcomes and Challenges ​

5.1 Success Rates and Long-term Outcomes ​

Islet cell transplantation has emerged as a significant therapeutic approach for the treatment of type 1 diabetes mellitus (T1DM), particularly for patients with severe complications or hypoglycemic unawareness. The procedure involves the isolation of islets from donor pancreases, which are then transplanted into the recipient's liver. This method aims to restore endogenous insulin production and improve glycemic control, thereby reducing or eliminating the need for exogenous insulin.

Clinical outcomes from islet transplantation have shown progressive improvements over the years. The Collaborative Islet Transplant Registry (CITR) reports indicate that insulin independence can be achieved in a substantial percentage of patients. Initially, prior to the Edmonton Protocol, only 9% of islet transplant recipients were insulin independent for more than one year. However, following the implementation of the Edmonton Protocol, insulin independence rates increased significantly, with recent studies reporting rates of 60% at one year post-transplantation[18].

Long-term outcomes are noteworthy as well. Although the rate of insulin independence tends to decline over time, the CITR data show that approximately 44% of patients remain insulin independent three years after the last infusion. Furthermore, some patients have achieved insulin independence for extended periods, with reports of over 13 years without insulin therapy[19]. The benefits of successful islet transplantation extend beyond insulin independence; patients often experience improved hypoglycemic awareness and a reduction in glycated hemoglobin levels, which can mitigate the chronic complications associated with diabetes, such as peripheral neuropathy and retinopathy[20].

Despite these advancements, several challenges persist in the field of islet transplantation. The primary obstacles include donor organ availability, the need for immunosuppressive therapy, and the risk of graft rejection. Immunosuppressive protocols, while necessary to prevent rejection, can lead to complications such as nephropathy and increased susceptibility to infections. Furthermore, the sustainability of insulin independence is variable, with factors such as the adequacy of islet mass and pre-transplant alloimmunity playing critical roles in the outcomes[21].

Emerging strategies are being explored to enhance the success rates of islet transplantation. These include refining immunosuppressive protocols, exploring alternative transplantation sites, and investigating new sources of islet cells, such as stem cells[3]. The development of hydrogel-encapsulated islet cells is also being researched as a means to improve graft survival and reduce immune responses[7].

In summary, islet cell transplantation represents a promising avenue for treating type 1 diabetes, with significant clinical outcomes and a growing body of evidence supporting its efficacy. However, challenges related to donor availability, immunosuppression, and long-term graft survival continue to necessitate ongoing research and innovation in this field.

5.2 Complications and Limitations ​

Islet cell transplantation has emerged as a promising therapeutic approach for treating diabetes, particularly type 1 diabetes mellitus (T1DM). This treatment aims to restore endogenous insulin production and improve glycometabolic control, potentially achieving insulin independence for patients. The clinical outcomes of islet transplantation have shown significant advancements, with insulin independence rates improving from 15% to 60% one year post-transplantation in recent years. Restoration of insulin secretion post-transplantation has been associated with enhanced quality of life, reduced hypoglycemic episodes, and a decrease in long-term diabetic complications[18].

Despite these promising outcomes, several challenges and limitations hinder the widespread adoption of islet transplantation as the gold standard treatment for T1DM. One of the primary obstacles is the limited availability of donor islets, which restricts the number of patients who can benefit from this procedure. Additionally, islet transplantation requires chronic immunosuppressive therapy to prevent graft rejection, which can lead to various complications, including increased susceptibility to infections and potential damage to other organs[21].

The engraftment of transplanted islets is another significant challenge. Factors such as sub-optimal oxygen supply, immune rejection, and the technical difficulties associated with islet isolation and transplantation can negatively impact islet survival. The need for multiple donors to achieve adequate islet mass further complicates the situation[22].

Emerging strategies to enhance the efficacy of islet transplantation include the use of hydrogel-encapsulated islet cells, which aim to improve graft survival by providing a protective environment against immune attack[7]. Furthermore, the incorporation of mesenchymal stem cells (MSCs) has been investigated to support islet graft survival, reduce immune-mediated rejection, and promote tissue repair and angiogenesis[23].

The future of islet transplantation may also involve exploring alternative transplantation sites, such as subcutaneous or intramuscular locations, which could potentially enhance islet graft survival and simplify immune regulation[3]. Advances in stem cell research, including the differentiation of stem cells into insulin-producing cells, may also provide new avenues to address the donor shortage and improve the overall success of islet transplantation[11].

In summary, while islet cell transplantation presents a viable option for treating diabetes, particularly T1DM, the clinical outcomes are tempered by significant challenges related to donor availability, immunosuppression-related complications, and islet engraftment issues. Ongoing research and innovative strategies are crucial to overcoming these limitations and enhancing the efficacy of this therapeutic approach.

6 Recent Advances and Future Directions ​

6.1 Innovations in Islet Preservation ​

Islet cell transplantation has emerged as a promising therapeutic approach for treating diabetes, particularly type 1 diabetes mellitus (T1DM). This procedure involves transplanting isolated islets from a donor pancreas into a recipient, aiming to restore endogenous insulin production and improve glycemic control. The recent advancements in islet transplantation highlight several innovations that address the challenges of islet preservation, transplantation techniques, and immunological responses.

The core benefit of islet transplantation lies in its ability to potentially achieve insulin independence for patients with T1DM. Studies have shown that successful islet transplantation can lead to significant improvements in glycemic control, prevention of severe hypoglycemia, and enhancement of overall quality of life [21]. Recent reports indicate that the rate of insulin independence one year post-transplantation has improved significantly, with some centers reporting rates as high as 60% compared to earlier rates of approximately 15% [18].

One of the major challenges in islet transplantation is the loss of islet cells during the isolation and transplantation processes, as well as post-transplantation immune rejection. Recent advancements have focused on improving islet preservation techniques to enhance cell viability and function. Innovations such as hydrogel encapsulation of islet cells have shown promise in protecting islets from immune rejection and oxidative stress, which are critical factors contributing to islet loss [7]. Hydrogel-encapsulated islet cells provide a supportive microenvironment that can improve graft survival and function, addressing the limitations of traditional transplantation methods [7].

Moreover, the exploration of alternative transplantation sites, such as the subcutaneous space and mesenteric fat, is gaining traction. These sites may offer advantages over the conventional portal vein approach by potentially reducing the risk of immunological complications and improving islet function [3]. Research into the immunological aspects of islet transplantation has also advanced, with the development of novel immunosuppressive protocols that aim to minimize the adverse effects associated with long-term immunosuppression [24].

The integration of stem cell research into islet transplantation is another exciting avenue that holds the potential to overcome the limitations of donor islet availability. Strategies to differentiate stem cells into insulin-producing cells could provide a renewable source of beta cells for transplantation, thus addressing the shortage of donor organs [11]. This approach not only aims to increase the availability of islets but also seeks to reduce or eliminate the need for lifelong immunosuppressive therapy, which is a significant drawback of current transplantation practices [10].

In summary, islet cell transplantation offers a viable solution for managing diabetes by restoring insulin production and improving glycemic control. Recent advances in islet preservation techniques, exploration of alternative transplantation sites, and the integration of stem cell technology represent critical innovations that may enhance the efficacy and accessibility of islet transplantation in the future. These developments are crucial in addressing the ongoing challenges in the field and in making islet transplantation a more widely accepted treatment option for diabetes.

6.2 Emerging Techniques in Transplantation ​

Islet cell transplantation represents a significant therapeutic strategy for treating diabetes, particularly type 1 diabetes mellitus (T1DM). This approach involves the transplantation of isolated islets from donor pancreases into diabetic recipients, with the aim of restoring endogenous insulin production and improving glycemic control. The procedure offers several advantages over traditional insulin therapy, including the potential for a more physiological regulation of blood glucose levels, reduced incidence of hypoglycemic episodes, and improved quality of life for patients.

Despite its promise, islet transplantation faces numerous challenges that limit its widespread application. One of the primary obstacles is the loss of islet cells before and after transplantation due to factors such as oxidative stress, immune rejection, and insufficient islet mass. It has been observed that islet survival is jeopardized during the isolation process, storage, and post-transplantation due to cellular damage and immune responses in diabetic patients (Yao et al., 2019)[4]. This highlights the necessity for protective strategies that can enhance islet viability and function.

Recent advances in transplantation techniques aim to address these challenges. For instance, the co-transplantation of mesenchymal stem cells (MSCs) alongside islets has shown promise in preclinical studies. MSCs may improve islet function through mechanisms such as immunomodulation and the promotion of angiogenesis, thereby enhancing graft survival and function (Sakata et al., 2011)[6]. Additionally, the encapsulation of islet cells in hydrogels is being explored as a method to shield them from immune attack and to create a more favorable microenvironment for islet survival post-transplantation (Huan et al., 2024)[7].

Furthermore, understanding the mechanisms underlying islet dysfunction and loss of β-cell function is critical. Studies have drawn parallels between the progressive loss of β-cell function in transplanted islets and that observed in type 2 diabetes, suggesting that similar therapeutic strategies could be beneficial in islet transplantation (Potter et al., 2014)[5]. This includes the exploration of incretin-based therapies that may serve as adjuncts to immunosuppressive regimens in islet transplantation.

Innovative transplantation sites are also being investigated to enhance islet graft survival. Traditional methods typically involve portal vein infusion, but alternative sites such as the subcutaneous space and mesenteric fat are being considered. These sites may offer better vascularization and reduced immune exposure, thus improving the longevity and function of transplanted islets (Wang et al., 2024)[3].

In summary, islet cell transplantation has the potential to effectively treat diabetes by restoring insulin production and improving metabolic control. However, to realize its full potential, ongoing research is essential to overcome current limitations, including donor shortages, immune rejection, and the development of effective strategies for islet preservation and transplantation. Emerging techniques such as MSC co-transplantation, hydrogel encapsulation, and novel transplantation sites hold promise for enhancing the success of islet transplantation in the future.

7 Conclusion ​

Islet cell transplantation has emerged as a transformative therapeutic strategy for treating diabetes, particularly type 1 diabetes mellitus (T1DM). The primary findings of this review indicate that islet transplantation can restore endogenous insulin production, significantly improve glycemic control, and enhance the quality of life for patients. Despite notable advancements, such as improved immunosuppressive protocols and innovative preservation techniques, challenges persist, including donor organ shortages, immune rejection, and the long-term viability of transplanted islets. The current research landscape reveals a promising trajectory toward overcoming these limitations through the exploration of alternative sources of islet cells, such as stem cells, and the development of encapsulation technologies that protect islets from immune attack. Future research should focus on optimizing transplantation techniques, refining immunosuppressive strategies, and enhancing the understanding of the immunological mechanisms at play. By addressing these challenges, islet transplantation could evolve into a more widely accessible and effective treatment option for diabetes, ultimately leading to improved outcomes and reduced complications for patients.

References ​

  • [1] Fritz Cayabyab;Lina R Nih;Eiji Yoshihara. Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes.. Frontiers in endocrinology(IF=4.6). 2021. PMID:34589059. DOI: 10.3389/fendo.2021.732431.
  • [2] Ryan M Jamiolkowski;Lucie Y Guo;Yun Rose Li;Sydney M Shaffer;Ali Naji. Islet transplantation in type I diabetes mellitus.. The Yale journal of biology and medicine(IF=3.9). 2012. PMID:22461742. DOI: .
  • [3] Qi Wang;Yu-Xi Huang;Long Liu;Xiao-Hong Zhao;Yi Sun;Xinli Mao;Shao-Wei Li. Pancreatic islet transplantation: current advances and challenges.. Frontiers in immunology(IF=5.9). 2024. PMID:38887292. DOI: 10.3389/fimmu.2024.1391504.
  • [4] Qing Yao;Xue Jiang;Longfa Kou;Adelaide T Samuriwo;He-Lin Xu;Ying-Zheng Zhao. Pharmacological actions and therapeutic potentials of bilirubin in islet transplantation for the treatment of diabetes.. Pharmacological research(IF=10.5). 2019. PMID:31054312. DOI: 10.1016/j.phrs.2019.104256.
  • [5] Kathryn J Potter;Clara Y Westwell-Roper;Agnieszka M Klimek-Abercrombie;Garth L Warnock;C Bruce Verchere. Death and dysfunction of transplanted β-cells: lessons learned from type 2 diabetes?. Diabetes(IF=7.5). 2014. PMID:24357689. DOI: 10.2337/db12-0364.
  • [6] Naoaki Sakata;Masafumi Goto;Gumpei Yoshimatsu;Shinichi Egawa;Michiaki Unno. Utility of co-transplanting mesenchymal stem cells in islet transplantation.. World journal of gastroenterology(IF=5.4). 2011. PMID:22215938. DOI: 10.3748/wjg.v17.i47.5150.
  • [7] Zhikun Huan;Jingbo Li;Zhiqiang Luo;Yunru Yu;Ling Li. Hydrogel-Encapsulated Pancreatic Islet Cells as a Promising Strategy for Diabetic Cell Therapy.. Research (Washington, D.C.)(IF=10.7). 2024. PMID:38966749. DOI: 10.34133/research.0403.
  • [8] Alison Anne Cotterell;Norma Sue Kenyon. Alternatives to immunosuppressive drugs in human islet transplantation.. Current diabetes reports(IF=6.4). 2002. PMID:12643199. DOI: 10.1007/s11892-002-0030-5.
  • [9] Emmanuel C Opara;William F Kendall. Immunoisolation techniques for islet cell transplantation.. Expert opinion on biological therapy(IF=4.0). 2002. PMID:12079486. DOI: 10.1517/14712598.2.5.503.
  • [10] R G Bretzel;M Eckhard;M D Brendel. Pancreatic islet and stem cell transplantation: new strategies in cell therapy of diabetes mellitus.. Panminerva medica(IF=4.3). 2004. PMID:15238879. DOI: .
  • [11] Juan Domínguez-Bendala;Camillo Ricordi. Present and future cell therapies for pancreatic beta cell replenishment.. World journal of gastroenterology(IF=5.4). 2012. PMID:23322984. DOI: 10.3748/wjg.v18.i47.6876.
  • [12] Toshihiro Nakamura;Junji Fujikura;Nobuya Inagaki. Advancements in transplantation therapy for diabetes: Pancreas, islet and stem cell.. Journal of diabetes investigation(IF=3.0). 2021. PMID:32654418. DOI: 10.1111/jdi.13358.
  • [13] Inderpal Singh Kochar;Rakhi Jain. Pancreas transplant in type 1 diabetes mellitus: the emerging role of islet cell transplant.. Annals of pediatric endocrinology & metabolism(IF=3.3). 2021. PMID:34218630. DOI: 10.6065/apem.2142012.006.
  • [14] Juris J Meier;Irene Hong-McAtee;Ryan Galasso;Johannes D Veldhuis;Antoinette Moran;Bernhard J Hering;Peter C Butler. Intrahepatic transplanted islets in humans secrete insulin in a coordinate pulsatile manner directly into the liver.. Diabetes(IF=7.5). 2006. PMID:16873697. DOI: 10.2337/db06-0069.
  • [15] Sulaiman A Nanji;A M James Shapiro. Islet transplantation in patients with diabetes mellitus: choice of immunosuppression.. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy(IF=6.9). 2004. PMID:15377174. DOI: 10.2165/00063030-200418050-00004.
  • [16] Manuela Battaglia;Angela Stabilini;Elena Draghici;Silvia Gregori;Cristina Mocchetti;Ezio Bonifacio;Maria-Grazia Roncarolo. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance.. Diabetes(IF=7.5). 2006. PMID:16380475. DOI: .
  • [17] A M James Shapiro;Sulaiman A Nanji;Jonathan R T Lakey. Clinical islet transplant: current and future directions towards tolerance.. Immunological reviews(IF=8.3). 2003. PMID:14617207. DOI: 10.1046/j.1600-065x.2003.00085.x.
  • [18] P Fiorina;A M J Shapiro;C Ricordi;A Secchi. The clinical impact of islet transplantation.. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons(IF=8.2). 2008. PMID:18828765. DOI: 10.1111/j.1600-6143.2008.02353.x.
  • [19] Paola Maffi;Antonio Secchi. Clinical results of islet transplantation.. Pharmacological research(IF=10.5). 2015. PMID:25931317. DOI: .
  • [20] Anthony Bruni;Boris Gala-Lopez;Andrew R Pepper;Nasser S Abualhassan;Am James Shapiro. Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges.. Diabetes, metabolic syndrome and obesity : targets and therapy(IF=3.0). 2014. PMID:25018643. DOI: 10.2147/DMSO.S50789.
  • [21] Simona Marzorati;Antonello Pileggi;Camillo Ricordi. Allogeneic islet transplantation.. Expert opinion on biological therapy(IF=4.0). 2007. PMID:17961088. DOI: 10.1517/14712598.7.11.1627.
  • [22] Mohsen Khosravi-Maharlooei;Ensiyeh Hajizadeh-Saffar;Yaser Tahamtani;Mohsen Basiri;Leila Montazeri;Keynoosh Khalooghi;Mohammad Kazemi Ashtiani;Ali Farrokhi;Nasser Aghdami;Anavasadat Sadr Hashemi Nejad;Mohammad-Bagher Larijani;Nico De Leu;Harry Heimberg;Xunrong Luo;Hossein Baharvand. THERAPY OF ENDOCRINE DISEASE: Islet transplantation for type 1 diabetes: so close and yet so far away.. European journal of endocrinology(IF=5.2). 2015. PMID:26036437. DOI: 10.1530/EJE-15-0094.
  • [23] Lisha Mou;Tony Bowei Wang;Xinyu Wang;Zuhui Pu. Advancing diabetes treatment: the role of mesenchymal stem cells in islet transplantation.. Frontiers in immunology(IF=5.9). 2024. PMID:38605972. DOI: 10.3389/fimmu.2024.1389134.
  • [24] A M James Shapiro. State of the art of clinical islet transplantation and novel protocols of immunosuppression.. Current diabetes reports(IF=6.4). 2011. PMID:21830042. DOI: 10.1007/s11892-011-0217-8.

MaltSci Intelligent Research Services ​

Search for more papers on MaltSci.com ​

Islet cell transplantation · Diabetes · Islet function · Immune modulation · Therapeutic strategies

© 2025 MaltSci