Lysophosphatidylinositols Are Upregulated After Human ß-Cell Loss and Potentiate Insulin Release.

In this study, we identified new lipid species associated with the loss of pancreatic ß-cells triggering diabetes. We performed lipidomics measurements on serum from prediabetic mice lacking ß-cell prohibitin-2 (a model of monogenic diabetes) patients without previous history of diabetes but scheduled for pancreaticoduodenectomy resulting in the acute reduction of their ß-cell mass (∼50%), and patients with type 2 diabetes (T2D). We found lysophosphatidylinositols (lysoPIs) were the main circulating lipid species altered in prediabetic mice. The changes were confirmed in the patients with acute reduction of their ß-cell mass and in those with T2D. Increased lysoPIs significantly correlated with HbA1c (reflecting glycemic control), fasting glycemia, and disposition index, and did not correlate with insulin resistance or obesity in human patients with T2D. INS-1E ß-cells as well as pancreatic islets isolated from nondiabetic mice and human donors exposed to exogenous lysoPIs showed potentiated glucose-stimulated and basal insulin secretion. Finally, addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. Overall, lysoPIs appear to be lipid species upregulated in the prediabetic stage associated with the loss of ß-cells and that support the secretory function of the remaining ß-cells. ARTICLE HIGHLIGHTS: Circulating lysophosphatidylinositols (lysoPIs) are increased in situations associated with ß-cell loss in mice and humans such as (pre-)diabetes, and hemipancreatectomy. Pancreatic islets isolated from nondiabetic mice and human donors, as well as INS-1E ß-cells, exposed to exogenous lysoPIs exhibited potentiated glucose-stimulated and basal insulin secretion. Addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. LysoPIs appear as lipid species being upregulated already in the prediabetic stage associated with the loss of ß-cells and supporting the function of the remaining ß-cells.

The Relevance of Advanced Therapy Medicinal Products in the Field of Transplantation and the Need for Academic Research Access: Overcoming Bottlenecks and Claiming a New Time.

The field of transplantation has witnessed the emergence of Advanced Therapy Medicinal Products (ATMPs) as highly promising solutions to address the challenges associated with organ and tissue transplantation. ATMPs encompass gene therapy, cell therapy, and tissue-engineered products, hold immense potential for breakthroughs in overcoming the obstacles of rejection and the limited availability of donor organs. However, the development and academic research access to ATMPs face significant bottlenecks that hinder progress. This opinion paper emphasizes the importance of addressing bottlenecks in the development and academic research access to ATMPs by implementing several key strategies. These include the establishment of streamlined regulatory processes, securing increased funding for ATMP research, fostering collaborations and partnerships, setting up centralized ATMP facilities, and actively engaging with patient groups. Advocacy at the policy level is essential to provide support for the development and accessibility of ATMPs, thereby driving advancements in transplantation and enhancing patient outcomes. By adopting these strategies, the field of transplantation can pave the way for the introduction of innovative and efficacious ATMP therapies, while simultaneously fostering a nurturing environment for academic research.

Intercellular contacts affect secretion and biosynthesis of pancreatic islet cells.

Cell protein biosynthesis is regulated by different factors, but implication of intercellular contacts on alpha and beta cell protein biosyntheses activity has not been yet investigated. Islet cell biosynthetic activity is essential in regulating not only the hormonal reserve within cells but also in renewing all the proteins involved in the control of secretion. Here we aimed to assess whether intercellular interactions affected similarly secretion and protein biosynthesis of rat alpha and beta cells. Insulin and glucagon secretion were analyzed by ELISA or reverse hemolytic plaque assay, and protein biosynthesis evaluated at single cell level using bioorthogonal noncanonical amino acid tagging. Regarding beta cells, we showed a positive correlation between insulin secretion and protein biosynthesis. We also observed that homologous contacts increased both activities at low or moderate glucose concentrations. By contrast, at high glucose concentration, homologous contacts increased insulin secretion and not protein biosynthesis. In addition, heterogeneous contacts between beta and alpha cells had no impact on insulin secretion and protein biosynthesis. Regarding alpha cells, we showed that when they were in contact with beta cells, they increased their glucagon secretion in response to a drop of glucose concentration, but, on the other hand, they decreased their protein biosynthesis under any glucose concentrations. Altogether, these results emphasize the role of intercellular contacts on the function of islet cells, showing that intercellular contacts increased protein biosynthesis in beta cells, except at high glucose, and decreased protein biosynthesis in alpha cells even when glucagon secretion is stimulated.

Identification of newly synthetized proteins by mass spectrometry to understand palmitate-induced early cellular changes in pancreatic islets.

Obesity and lipid metabolism dysregulation are often associated with insulin resistance, and can lead to type 2 diabetes. However, mechanisms linking insulin resistance, high levels of plasma free fatty acids (FFA), and ß cell failure remain unclear. The aim of this work was to search for proteins whose synthesis was modified by a short exposure to FFA. This could help in the future to identify molecular mechanisms underlying islet dysfunction in the presence of FFA. Therefore, we assessed by mass spectrometry de novo protein synthesis of freshly isolated rat islets after palmitate short exposure. Quantitative proteome and secretome analyses were performed by combining metabolic incorporation of azidohomoalanine (AHA) and pulse labeling with stable isotope labeling by amino acids in cell culture (SILAC). We showed that pancreatic islets, in response to 4-h exposure to palmitate, increased the synthesis of ribosomal proteins and proteins of the cytoskeleton, and increased their secretion of proteins involved in insulin synthesis and insulin secretion, as well as insulin itself. First, these results show that de novo protein quantification analysis by LC-MS/MS is a useful method to investigate cellular modifications induced by FFA on pancreatic islets. Also, these results show that short exposure to palmitate increases the expression of ribosomal proteins and proteins involved in insulin secretion, and it remains to be determined if these effects are responsible or linked to the harmful effect of palmitate on ß cells.NEW & NOTEWORTHY These results show that pancreatic rat islets cultured with palmitate mainly increase synthesis of ribosomal proteins and some proteins of the cytoskeleton. They also show a significant increase of secreted proteins involved in insulin synthesis and insulin secretion, as well as insulin itself. These data provide information to understand the mechanisms of ß cell failure induced by lipotoxicity via the identification of all newly synthesized proteins in islets in response to short-term exposure to palmitate.

Guidelines to Analyze Preclinical Studies Using Perinatal Derivatives.

The last 18 years have brought an increasing interest in the therapeutic use of perinatal derivatives (PnD). Preclinical studies used to assess the potential of PnD therapy include a broad range of study designs. The COST SPRINT Action (CA17116) aims to provide systematic and comprehensive reviews of preclinical studies for the understanding of the therapeutic potential and mechanisms of PnD in diseases and injuries that benefit from PnD therapy. Here we describe the publication search and data mining, extraction, and synthesis strategies employed to collect and prepare the published data selected for meta-analyses and reviews of the efficacy of PnD therapies for different diseases and injuries. A coordinated effort was made to prepare the data suitable to make statements for the treatment efficacy of the different types of PnD, routes, time points, and frequencies of administration, and the dosage based on clinically relevant effects resulting in clear increase, recovery or amelioration of the specific tissue or organ function. According to recently proposed guidelines, the harmonization of the nomenclature of PnD types will allow for the assessment of the most efficient treatments in various disease models. Experts within the COST SPRINT Action (CA17116), together with external collaborators, are doing the meta-analyses and reviews using the data prepared with the strategies presented here in the relevant disease or research fields. Our final aim is to provide standards to assess the safety and clinical benefit of PnD and to minimize redundancy in the use of animal models following the 3R principles for animal experimentation.

Generation of Insulin-Producing Multicellular Organoids.

Clinical islet transplantation (CIT) is an established noninvasive treatment for type I diabetes (T1D) and has demonstrated improved glycemic control, preventing the occurrence of severe hypoglycemia. However, CIT has several limitations, such as the need for multiple donors, lifelong immunosuppression, and suboptimal long-term graft function. Most of the transplanted islets are lost due to inflammation, ischemic damage, and delayed revascularization.Generation of organoids have gained increasing interest in regenerative medicine in recent years. In the context of beta-cell replacement, it offers a possibility to address limitations of CIT by allowing to produce uniform organoids from single or multiple cell types facilitating revascularization and anti-inflammatory and/or immunomodulatory protection. We have previously generated multicellular insulin-secreting organoids composed of islet cells and the human amniotic epithelial cells (hAECs). These 3D insulin-secreting structures demonstrated improved viability and function both in vitro and in vivo. Here we detail a stepwise methodology to generate insulin-secreting organoids using two different methods. In addition, quality assessment in vitro tests are also described.

From islet of Langerhans transplantation to the bioartificial pancreas.

Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe secondary complications, in particular end-stage nephropathy, or life-threatening severe hypoglycemia, the best therapeutic approach is pancreas transplantation, or more recently transplantation of the pancreatic islets of Langerhans. Islet transplantation is a cell therapy procedure, that is minimally invasive and has a low morbidity, but does not display the same rate of functional success as the more invasive pancreas transplantation because of suboptimal engraftment and survival. Another issue is that pancreas or islet transplantation (collectively known as beta cell replacement therapy) is limited by the shortage of organ donors and by the need for lifelong immunosuppression to prevent immune rejection and recurrence of autoimmunity. A bioartificial pancreas is a construct made of functional, insulin-producing tissue, embedded in an anti-inflammatory, immunomodulatory microenvironment and encapsulated in a perm-selective membrane allowing glucose sensing and insulin release, but isolating from attacks by cells of the immune system. A successful bioartificial pancreas would address the issues of engraftment, survival and rejection. Inclusion of unlimited sources of insulin-producing cells, such as xenogeneic porcine islets or stem cell-derived beta cells would further solve the problem of organ shortage. This article reviews the current status of clinical islet transplantation, the strategies aiming at developing a bioartificial pancreas, the clinical trials conducted in the field and the perspectives for further progress.

Mechanisms of Immunomodulation and Cytoprotection Conferred to Pancreatic Islet by Human Amniotic Epithelial Cells.

Inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. Human amniotic epithelial cells (hAECs) possess regenerative, immunomodulatory and anti-inflammatory properties. We hypothesized that hAECs could protect islets from cellular damage induced by pro-inflammatory cytokines. To verify our hypothesis, hAEC monocultures, rat islets (RI), or RI-hAEC co-cultures where exposed to a pro-inflammatory cytokine cocktail (Interferon γ: IFN-γ, Tumor necrosis factor α: TNF-α and Interleukin-1ß: IL-1ß). The secretion of anti-inflammatory cytokines and gene expression changes in hAECs and viability and function of RI were evaluated. The expression of non-classical Major Histocompatibility Complex (MHC) class I molecules by hAECs cultured with various IFN-γ concentrations were assessed. Exposure to the pro-inflammatory cocktail significantly increased the secretion of the anti-inflammatory cytokines IL6, IL10 and G-CSF by hAECs, which was confirmed by upregulation of IL6, and IL10 gene expression. HLA-G, HLA-E and PDL-1 gene expression was also increased. This correlated with an upregulation of STAT1, STAT3 and NF-κB1gene expression levels. RI co-cultured with hAECs maintained normal function after cytokine exposure compared to RI cultured alone, and showed significantly lower apoptosis rate. Our results show that exposure to pro-inflammatory cytokines stimulates secretion of anti-inflammatory and immunomodulatory factors by hAECs through the JAK1/2 - STAT1/3 and the NF-κB1 pathways, which in turn protects islets against inflammation-induced damages. Integrating hAECs in islet transplants appears as a valuable strategy to achieve to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing reducing systemic immunosuppressive regimens. This study focuses on the cytoprotective effect of isolated hAECs on islets exposed to pro-inflammatory cytokines in vitro. Exposure to pro-inflammatory cytokines stimulated secretion of anti-inflammatory and immunomodulatory factors by hAECs putatively through the JAK1/2 - STAT1/3 and the NF-κB1 pathways. This had protective effect on islets against inflammation-induced damages. Taken together our results indicate that incorporating hAECs in islet transplants could be a valuable strategy to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing to reduce systemic immunosuppressive regimens.

The Role and Clinical Interest of Extracellular Vesicles in Pregnancy and Ovarian Cancer.

Ovarian cancer and pregnancy are two states in which the host immune system is exposed to novel antigens. Indeed, both the tumor and placenta must invade tissues, remodel vasculature to establish a robust blood supply, and evade detection by the immune system. Interestingly, tumor and placenta tissue use similar mechanisms to induce these necessary changes. One mediator is emerging as a key player in invasion, vascular remodeling, and immune evasion: extracellular vesicles (EVs). Many studies have identified EVs as a key mediator of cell-to-cell communication. Specifically, the cargo carried by EVs, which includes proteins, nucleic acids, and lipids, can interact with cells to induce changes in the target cell ranging from gene expression to migration and metabolism. EVs can promote cell division and tissue invasion, immunosuppression, and angiogenesis which are essential for both cancer and pregnancy. In this review, we examine the role of EVs in ovarian cancer metastasis, chemoresistance, and immune modulation. We then focus on the role of EVs in pregnancy with special attention on the vascular remodeling and regulation of the maternal immune system. Lastly, we discuss the clinical utility of EVs as markers and therapeutics for ovarian cancer and pre-eclampsia.

Mini-organs forum: how to advance organoid technology to organ transplant community.

The generation of human mini-organs, the so-called organoids, is one of the biggest scientific advances in regenerative medicine. This technology exploits traditional three-dimensional culture techniques that support cell-autonomous self-organization responses of stem cells to derive micrometer to millimeter size versions of human organs. The convergence of the organoid technology with organ transplantation is still in its infancy but this alliance is expected to open new venues to change the way we conduct both transplant and organoid research. In this Forum we provide a summary on early achievements facilitating organoid derivation and culture. We further discuss on early advances of organoid transplantation also offering a comprehensive overview of current limitations and challenges to instruct organoid maturation. We expect that this Forum sets the ground for initial discussions between stem cell biologists, bioengineers, and the transplant community to better direct organoid basic research to advance the organ transplantation field.

An inhibitor-mediated beta-cell dedifferentiation model reveals distinct roles for FoxO1 in glucagon repression and insulin maturation.

OBJECTIVE: The loss of forkhead box protein O1 (FoxO1) signaling in response to metabolic stress contributes to the etiology of type II diabetes, causing the dedifferentiation of pancreatic beta cells to a cell type reminiscent of endocrine progenitors. Lack of methods to easily model this process in vitro, however, have hindered progress into the identification of key downstream targets and potential inhibitors. We therefore aimed to establish such an in vitro cellular dedifferentiation model and apply it to identify novel agents involved in the maintenance of beta-cell identity. METHODS: The murine beta-cell line, Min6, was used for primary experiments and high-content screening. Screens encompassed a library of small-molecule drugs representing the chemical and target space of all FDA-approved small molecules with an automated immunofluorescence readout. Validation experiments were performed in a murine alpha-cell line as well as in primary murine and human diabetic islets. Developmental effects were studied in zebrafish and C. elegans models, while diabetic db/db mouse models were used to elucidate global glucose metabolism outcomes. RESULTS: We show that short-term pharmacological FoxO1 inhibition can model beta-cell dedifferentiation by downregulating beta-cell-specific transcription factors, resulting in the aberrant expression of progenitor genes and the alpha-cell marker glucagon. From a high-content screen, we identified loperamide as a small molecule that can prevent FoxO inhibitor-induced glucagon expression and further stimulate insulin protein processing and secretion by altering calcium levels, intracellular pH, and FoxO1 localization. CONCLUSIONS: Our study provides novel models, molecular targets, and drug candidates for studying and preventing beta-cell dedifferentiation.

[Total pancreatectomy and islet auto-transplantation: current state and new perspectives]. / Pancréatectomie totale et autotransplantation d'îlots†: état actuel et nouvelles perspectives.

Total pancreatectomy is a procedure primarily performed for chronic pancreatitis refractory to conservative therapy. It may nevertheless be indicated in the event of a malignant tumor, either as a treatment for a surgical complication or as a prevention of anastomotic leakage. If possible, islet auto-transplantation should be combined with total pancreatectomy for benign disease, in order to prevent a severe diabetes. Until recently, malignant disease was considered an absolute contraindication to islet auto-transplantation. A recent series from Milan showed promising oncological results in auto-transplantation for malignant disease, opening up new perspectives for total pancreatectomy for cancer.

La pancréatectomie totale est une procédure principalement effectuée pour une pancréatite chronique réfractaire au traitement conservateur. Elle peut néanmoins être indiquée en cas de tumeur maligne, soit comme traitement d'une complication chirurgicale, soit en prévention de fuite anastomotique. Dans la mesure du possible, une autogreffe d'îlots de Langerhans devrait être associée à une pancréatectomie totale pour maladie bénigne, dans le but de prévenir un diabète pancréatoprive. Jusqu'à récemment, une pathologie maligne était considérée comme une contre-indication absolue à une autogreffe d'îlots. Une série récente de Milan a montré des résultats oncologiques prometteurs en cas d'autogreffe pour pathologies malignes, ouvrant de nouvelles perspectives à la pancréatectomie totale pour cancer.

Failure mode and effect analysis in human islet isolation: from the theoretical to the practical risk.

This study aimed to assess the global mapping risk of human islet isolation, using a failure mode and effect analysis (FMEA), and highlight the impact of quality assurance procedures on the risk level of criticality. Risks were scored using the risk priority number (RPN) scoring method. The risk level of criticality was made based on RPN and led to risk classification (low to critical). A raw risk analysis and a risk control analysis (with control means and quality assurance performance) were undertaken. The process of human islet isolation was divided into 11 steps, and 230 risks were identified. Analysis of the highest RPN of each of the 11 steps showed that the 4 highest risks were related to the pancreas digestion and islet purification stages. After implementation of reduction measures and controls, critical and severe risks were reduced by 3-fold and by 2-fold, respectively, so that 90% of risks could be considered as low to moderate. FMEA has proven to be a powerful approach for the identification of weaknesses in the islet isolation processes. The results demonstrated the importance of staff qualification and continuous training and supported the contribution of the quality assurance system to risk reduction.

Bio-Engineering of Pre-Vascularized Islet Organoids for the Treatment of Type 1 Diabetes.

Lack of rapid revascularization and inflammatory attacks at the site of transplantation contribute to impaired islet engraftment and suboptimal metabolic control after clinical islet transplantation. In order to overcome these limitations and enhance engraftment and revascularization, we have generated and transplanted pre-vascularized insulin-secreting organoids composed of rat islet cells, human amniotic epithelial cells (hAECs), and human umbilical vein endothelial cells (HUVECs). Our study demonstrates that pre-vascularized islet organoids exhibit enhanced in vitro function compared to native islets, and, most importantly, better engraftment and improved vascularization in vivo in a murine model. This is mainly due to cross-talk between hAECs, HUVECs and islet cells, mediated by the upregulation of genes promoting angiogenesis (vegf-a) and ß cell function (glp-1r, pdx1). The possibility of adding a selected source of endothelial cells for the neo-vascularization of insulin-scereting grafts may also allow implementation of ß cell replacement therapies in more favourable transplantation sites than the liver.

Treatment of COVID-19 Pneumonia: the Case for Placenta-derived Cell Therapy.

Nearly 500'000 fatalities due to COVID-19 have been reported globally and the death toll is still rising. Most deaths are due to acute respiratory distress syndrome (ARDS), as a result of an excessive immune response and a cytokine storm elicited by severe SARS-CoV-2 lung infection, rather than by a direct cytopathic effect of the virus. In the most severe forms of the disease therapies should aim primarily at dampening the uncontrolled inflammatory/immune response responsible for most fatalities. Pharmacological agents - antiviral and anti-inflammatory molecules - have not been able so far to achieve compelling results for the control of severe COVID-19 pneumonia. Cells derived from the placenta and/or fetal membranes, in particular amniotic epithelial cells (AEC) and decidual stromal cells (DSC), have established, well-characterized, potent anti-inflammatory and immune-modulatory properties that make them attractive candidates for a cell-based therapy of COVID19 pneumonia. Placenta-derived cells are easy to procure from a perennial source and pose minimal ethical issues for their utilization. In view of the existing clinical evidence for the innocuousness and efficiency of systemic administration of DSCs or AECs in similar conditions, we advocate for the initiation of clinical trials using this strategy in the treatment of severe COVID-19 disease.

Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion.

A correct biosynthetic activity is thought to be essential for the long-term function and survival of islet cells in culture and possibly also after islet transplantation. Compared to the secretory activity, biosynthetic activity has been poorly studied in pancreatic islet cells. Here we aimed to assess biosynthetic activity at the single cell level to investigate if protein synthesis is dependent on secretagogues and increased as a consequence of hormonal secretion. Biosynthetic activity in rat islet cells was studied at the single cell level using O-propargyl-puromycin (OPP) that incorporates into newly translated proteins and chemically ligates to a fluorescent dye by "click" reaction. Heterogeneous biosynthetic activity was observed between the four islet cell types, with delta cells showing the higher relative protein biosynthesis. Beta cells protein biosynthesis was increased in response to glucose while 3-isobutyl-1-methylxanthine and phorbol-12-myristate-13-acetate, 2 drugs known to stimulate insulin secretion, had no similar effect on protein biosynthesis. However, after several hours of secretion, protein biosynthesis remained high even when cells were challenged to basal conditions. These results suggest that mechanisms regulating secretion and biosynthesis in islet cells are different, with glucose directly triggering beta cells protein biosynthesis, independently of insulin secretion. Furthermore, this OPP labeling approach is a promising method to identify newly synthesized proteins under various physiological and pathological conditions.

Impact of ischemia time on islet isolation success and posttransplantation outcomes: A retrospective study of 452 pancreas isolations.

Many variables impact islet isolation, including pancreas ischemia time. The ischemia time upper limit that should be respected to avoid a negative impact on the isolation outcome is not well defined. We have performed a retrospective analysis of all islet isolations in our center between 2008 and 2018. Total ischemia time, cold ischemia time, and organ removal time were analyzed. Isolation success was defined as an islet yield ≥200 000 IEQ. Of the 452 pancreases included, 288 (64%) were successfully isolated. Probability of isolation success showed a significant decrease after 8 hours of total ischemia time, 7 hours of cold ischemia time, and 80 minutes of organ removal time. Although we observed an impact of ischemia time on islet yield, a probability of isolation success of 50% was still present even when total ischemia time exceeds 12 hours. Posttransplantation clinical outcomes were assessed in 32 recipients and no significant difference was found regardless of ischemia time. These data indicate that although shorter ischemia times are associated with better islet isolation outcomes, total ischemia time >12 hours can provide excellent results in appropriately selected donors.

[Insulin-secreting organoids: a first step towards the bioartificial pancreas]. / Organoïdes sécréteurs d'insuline - Des « super-îlots ¼ comme premier pas vers le pancréas bioartificiel.

Pancreatic islet transplantation is a valid cure for selected type-1 diabetic patients. It offers a minimally invasive ß-cell replacement approach and has proven its capacity to significantly enhance patients quality of life. However, these insulin-secreting mini-organs suffer from the loss of intrinsic vascularization and extra-cellular matrix occurring during isolation, resulting in hypoxic stress and necrosis. In addition, they have to face inflammatory and immune destruction once transplanted in the liver. Organoid generation represents a strategy to overcome these obstacles by allowing size and shape control as well as composition. It does offer the possibility to add supporting cells such as endothelial cells, in order to facilitate revascularization or cells releasing anti-inflammatory and/or immunomodulatory factors. This review describes the limitations of pancreatic islet transplantation and details the benefits offered by organoids as a cornerstone toward the generation of a bioartificial pancreas.

TITLE: Organoïdes sécréteurs d'insuline - Des « super-îlots ¼ comme premier pas vers le pancréas bioartificiel. ABSTRACT: La greffe d'îlots pancréatiques permet de remplacer les cellules ß de manière minimalement invasive1, et d'améliorer significativement la qualité de vie des patients présentant un diabète de type 1. Cependant, ces mini-organes endocriniens, lorsqu'ils sont transplantés après une procédure d'extraction enzymatique du pancréas, se retrouvent déconnectés de leur vascularisation et de leur support fonctionnel. Les îlots doivent de plus faire face aux attaques des systèmes immunitaires inné et adaptatif, ainsi qu'à la récidive de l'auto-immunité. L'utilisation et la création d'organoïdes produisant et sécrétant de l'insuline permettent non seulement de contrôler et d'homogénéiser leur taille, mais également leur composition, avec la possibilité d'ajouter des cellules essentielles à leur survie, telles que des cellules endothéliales ou des cellules possédant des propriétés anti-inflammatoires et immuno-modulatrices. Dans cette revue, nous décrivons les obstacles rencontrés dans la greffe d'îlots et détaillons les bénéfices de l'utilisation d'organoïdes pour les surmonter.

Author Correction: Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.