Correction: Balaphas et al. Cell Therapy for Anal Sphincter Incontinence: Where Do We Stand? Cells 2021, 10, 2086.

The authors would like to add a new reference to the section "3 [...].

Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets.

OBJECTIVE: Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application. To find a new strategy, we tested a new polymer combination for islet encapsulation and transplantation. Meanwhile, we explored a new site for xenogeneic islet transplantation in mice. METHOD: We synthesized a hydrogel combining alginate plus poly-ethylene-imine (Alg/PEI) for the encapsulation of rat, neonatal porcine, and human islets. Transplantation was performed into the retroperitoneal retro-colic space of diabetic mice. Control mice received free islets under the kidney capsule or encapsulated islets into the peritoneum. The biochemical indexes were measured, and the transplanted islets were harvested for immunohistochemical staining of insulin and glucagon. RESULTS: Mice receiving encapsulated rat, porcine and human islets transplanted into the retroperitoneal space maintained normoglycemia for a median of 275, 145.5, and 146 days, respectively. In contrast, encapsulated xenogeneic islets transplanted into the peritoneum, maintained function for a median of 61, 95.5, and 82 days, respectively. Meanwhile, xenogeneic islets transplanted free into the kidney capsule lost their function within 3 days after transplantation. Immunohistochemical staining of encapsulated rat, porcine and human islets, retrieved from the retroperitoneal space, allowed to distinguish morphological normal insulin expressing ß- and glucagon expressing α-cells at 70, 60, and 100 days post-transplant, respectively. CONCLUSION: Transplantation of Alg/PEI encapsulated xenogeneic islets into the retroperitoneal space provides a valuable new implantation strategy for the treatment of type 1 diabetes.

Isolation and Characterization of Stem Cells from the Anal Canal Transition Zone in Pigs.

BACKGROUND: Utilization of autologous stem cells has been proposed for the treatment of anal incontinence despite a lack of understanding of their mechanism of action and of the physiological healing process of anal sphincters after injury. AIMS: We aim to develop a technique allowing isolation and further study of local mesenchymal stem cells, directly from anal canal transition zone in pig. METHODS: Anal canal was resected "en bloc" from two young pigs and further microdissected. The anal canal transition zone was washed and digested with 0.1% type I collagenase for 45 min at 37 °C. The isolated cells were plated on dishes in mesenchymal stem cell medium and trypsinized when confluent. Cells were further used for flow cytometry analysis and differentiation assays. RESULTS: The anal canal transition zone localization was confirmed with H&E staining. Following culture, cells exhibited a typical "fibroblast-like" morphology typical of stem cells. Isolated cells were positive for CD90 and CD44 but negative for CD14, CD34, CD45, CD105, CD106, and SLA-DR. Following incubation with specific differentiation medium, isolated cells differentiated into adipocytes, osteoblasts, and chondrocytes, confirming in vitro multipotency. CONCLUSIONS: Herein, we report for the first time the presence of mesenchymal stem cells in the anal canal transition zone in pigs and the feasibility of their isolation. This preliminary study opens the path to the isolation of human anal canal transition zone mesenchymal stem cells that might be used to study sphincters healing and to treat anal incontinence.

Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps.

Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future.

Engineering Islets From Stem Cells: The Optimal Solution for the Treatment of Diabetes?

Diabetes is a metabolic disease characterized by insulin deficiency. Bioengineering of stem cells with the aim to restore insulin production and glucose regulation has the potential to cure diabetic patients. In this review, we focus on the recent developments for bioengineering of induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and pancreatic progenitor cells in view of generating insulin producing and glucose regulating cells for ß-cell replacement therapies. Recent clinical trials using islet cells derived from stem cells have been initiated for the transplantation into diabetic patients, with crucial bottlenecks of tumorigenesis, post-transplant survival, genetic instability, and immunogenicity that should be further optimized. As a new approach given high expectations, bioengineered islets from stem cells occupies considerable potential for the future clinical application and addressing the treatment dilemma of diabetes.

Optimized Isolation and Characterization of C57BL/6 Mouse Hepatic Stellate Cells.

To obtain meaningful results of hepatic stellate cell (HSC) function, it is crucial to use highly pure HSC populations. Our aim was to optimize HSC isolation from mice livers without exploiting the characteristically transient vitamin A autofluorescence of HSC. HSCs were isolated from C57BL/6 mice using a two-step collagenase digestion and Nycodenz gradient separation followed by CD11b-negative sorting step in order to remove contaminating macrophages and dendritic cells. Isolated cells were analyzed for yield, viability, purity, and potential new markers using immunofluorescence and flow cytometry. We obtained a yield of 350,595 ± 100,773 HSC per mouse liver and a viability of isolated cells of 92.4 ± 3.1%. We observed a low macrophage/dendritic cell contamination of 1.22 ± 0.54%. Using flow cytometry, we demonstrated that CD38 was expressed at the surface of HSC subpopulations and that all expressed intracellular markers specific for HSC in the liver. This isolation method, avoiding fluorescent activated cell sorting (FACS), allowed isolation of HSCs with high purity. Further, flow cytometry analysis suggests that CD38 may be a reliable marker of HSCs and may include subpopulations of HSCs without retinoid droplets.

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes.

Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression. In recent years, a variety of engineering strategies have been developed to improve the composition and properties of encapsulation materials and to explore the clinical practicality of islet cell transplantation from different sources. In particular, the encapsulation of porcine islet and the co-encapsulation of islet cells with other by-standing cells or active ingredients for promoting long-term functionality, attracted significant research efforts. Hydrogels have been widely used for cell encapsulation as well as other therapeutic applications including tissue engineering, cell carriers or drug delivery. Here, we review the current status of various hydrogel biomaterials, natural and synthetic, with particular focus on islet transplantation applications. Natural hydrophilic polymers include polysaccharides (starch, cellulose, alginic acid, hyaluronic acid, chitosan) and peptides (collagen, poly-L-lysine, poly-L-glutamic acid). Synthetic hydrophilic polymers include alcohol, acrylic acid and their derivatives [poly (acrylic acid), poly (methacrylic acid), poly(acrylamide)]. By understanding the advantages and disadvantages of materials from different sources and types, appropriate materials and encapsuling methods can be designed and selected as needed to improve the efficacy and duration of islet. Islet capsule transplantation is emerging as a promising future treatment for T1D.

Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function.

Type 1 diabetes (T1D) is a widespread disease, affecting approximately 41.5 million people worldwide. It is generally treated with exogenous insulin, maintaining physiological blood glucose levels but also leading to long-term therapeutic complications. Pancreatic islet cell transplantation offers a potential alternative treatment to insulin injections. Shortage of human organ donors has raised the interest for porcine islet xenotransplantation. Neonatal porcine islets are highly available, can proliferate and mature in vitro as well as after transplantation in vivo. Despite promising preclinical results, delayed insulin secretion caused by immaturity and immunogenicity of the neonatal porcine islets remains a challenge for their clinical application. Multipotent mesenchymal stromal cells (MSCs) are known to have pro-angiogenic, anti-inflammatory and immunomodulatory effects. The current state of research emphasizes the great potential of co-culture and co-transplantation of islet cells with MSCs. Studies have shown enhanced islet proliferation and maturation, insulin secretion and graft survival, resulting in an improved graft outcome. This review summarizes the immunomodulatory and anti-inflammatory properties of MSC in the context of islet transplantation.

International Human Xenotransplantation Inventory: A 10-year Follow-up.

BACKGROUND: Following the recommendations by a panel of experts gathered by the World Health Organization in 2005, an inventory was established to collect practices of human xenotransplantation worldwide ( www.humanxenotransplant.org ). The website was activated in October 2006, in collaboration with the International Xenotransplantation Association, the University Hospital Geneva, and the World Health Organization. A first report on the collected xenotransplantation activities was published in 2010 in the journal Transplantation . In 2020, the website was redesigned, and its hosting and management were transferred to the Sichuan Provincial People's Hospital. METHODS: We collected information from publications in scientific journals, presentations at international congresses, the internet, and declarations of International Xenotransplantation Association members on xenotransplantation procedures in humans performed over the past 10 y. RESULTS: A total of 5 new applications of human xenotransplantation were identified, with pig as source animal in all applications. The procedures involved transplantation of islets of Langerhans, skin, cornea, and choroid plexus cells. The treatments were performed in China, United States, New Zealand, and Argentina. No major complications or deaths were reported. CONCLUSIONS: Several clinical applications of cell or tissue xenotransplantation are ongoing around the world. Compared with the previous reported period (1995-2010, with 29 activities, mostly without governmental regulation), the recent number of clinical activities was reduced, and all were officially approved. This information should be used to inform healthcare officials, staff, and the public with the objective of encouraging good practices based on internationally harmonized guidelines driven by initiatives such as the Changsha Communiqué.

Cell Therapy for Anal Sphincter Incontinence: Where Do We Stand?

Anal sphincter incontinence is a chronic disease, which dramatically impairs quality of life and induces high costs for the society. Surgery, considered as the best curative option, shows a disappointing success rate. Stem/progenitor cell therapy is pledging, for anal sphincter incontinence, a substitute to surgery with higher efficacy. However, the published literature is disparate. Our aim was to perform a review on the development of cell therapy for anal sphincter incontinence with critical analyses of its pitfalls. Animal models for anal sphincter incontinence were varied and tried to reproduce distinct clinical situations (acute injury or healed injury with or without surgical reconstruction) but were limited by anatomical considerations. Cell preparations used for treatment, originated, in order of frequency, from skeletal muscle, bone marrow or fat tissue. The characterization of these preparations was often incomplete and stemness not always addressed. Despite a lack of understanding of sphincter healing processes and the exact mechanism of action of cell preparations, this treatment was evaluated in 83 incontinent patients, reporting encouraging results. However, further development is necessary to establish the correct indications, to determine the most-suited cell type, to standardize the cell preparation method and to validate the route and number of cell delivery.

Therapeutic targeting of STAT3 pathways in pancreatic adenocarcinoma: A systematic review of clinical and preclinical literature.

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma is a highly lethal disease with increasing incidence. Due to high resistance, chemo/radiotherapy has limited success in pancreatic cancer and only marginally prolongs patient survival. Therefore, novel biomarkers and therapeutic targets are needed. In the present review, we performed a comprehensive summary of therapeutic approaches targeting the GP130/JAK/STAT3 pathway. METHODS: We systematically reviewed the PubMed and Embase databases for preclinical and clinical studies, from inception to October 4, 2020, on drugs targeting the GP130/JAK/STAT3 pathway. Bias assessments and qualitative analyses were performed. RESULTS: Twenty-five preclinical and nine clinical trials were included in the review. All preclinical studies reported a favorable outcome in terms of pancreatic ductal adenocarcinoma progression. Futhermore, drugs targeting the GP130/JAK/STAT3 pathway were shown to be efficient chemosensitizers. However, high publication bias was assumed. In the clinical setting, bazedoxifene and itacitinib improved patient outcomes. CONCLUSION: Preclinical studies strongly suggest significant efficacy of drugs targeting GP130/JAK/STAT3 in the treatment of pancreatic ductal adenocarcinoma and that these molecules are effective chemosensitizers. Though only a few trials have shown the efficacy in a clinical setting, the STAT3 pathway remains a promising drug target for future treatment of pancreatic ductal adenocarcinoma and may help overcome chemotherapy resistance.

Asymmetrical Forces Dictate the Distribution and Morphology of Platelets in Blood Clots.

Primary hemostasis consists in the activation of platelets, which spread on the exposed extracellular matrix at the injured vessel surface. Secondary hemostasis, the coagulation cascade, generates a fibrin clot in which activated platelets and other blood cells get trapped. Active platelet-dependent clot retraction reduces the clot volume by extruding the serum. Thus, the clot architecture changes with time of contraction, which may have an important impact on the healing process and the dissolution of the clot, but the precise physiological role of clot retraction is still not completely understood. Since platelets are the only actors to develop force for the retraction of the clot, their distribution within the clot should influence the final clot architecture. We analyzed platelet distributions in intracoronary thrombi and observed that platelets and fibrin co-accumulate in the periphery of retracting clots in vivo. A computational mechanical model suggests that asymmetric forces are responsible for a different contractile behavior of platelets in the periphery versus the clot center, which in turn leads to an uneven distribution of platelets and fibrin fibers within the clot. We developed an in vitro clot retraction assay that reproduces the in vivo observations and follows the prediction of the computational model. Our findings suggest a new active role of platelet contraction in forming a tight fibrin- and platelet-rich boundary layer on the free surface of fibrin clots.

Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters.

Neonatal and juvenile porcine islet cell clusters (ICC) present an unlimited source for islet xenotransplantation to treat type 1 diabetes patients. We isolated ICC from pancreata of 14 days old juvenile piglets and characterized their maturation by immunofluorescence and insulin secretion assays. Multipotent mesenchymal stromal cells derived from exocrine tissue of same pancreata (pMSC) were characterized for their differentiation potential and ability to sustain ICC insulin secretion in vitro and in vivo. Isolation of ICC resulted in 142 ± 50 × 103 IEQ per pancreas. Immunofluorescence staining revealed increasing presence of insulin-positive beta cells between day 9 and 21 in culture and insulin content per 500IEC of ICC increased progressively over time from 1178.4 ± 450 µg/L to 4479.7 ± 1954.2 µg/L from day 7 to 14, P < .001. Highest glucose-induced insulin secretion by ICC was obtained at day 7 of culture and reached a fold increase of 2.9 ± 0.4 compared to basal. Expansion of adherent cells from the pig exocrine tissue resulted in a homogenous CD90+ , CD34- , and CD45- fibroblast-like cell population and differentiation into adipocytes and chondrocytes demonstrated their multipotency. Insulin release from ICC was increased in the presence of pMSC and dependent on cell-cell contact (glucose-induced fold increase: ICC alone: 1.6 ± 0.2; ICC + pMSC + contact: 3.2 ± 0.5, P = .0057; ICC + pMSC no-contact: 1.9 ± 0.3; theophylline stimulation: alone: 5.4 ± 0.7; pMSC + contact: 8.4 ± 0.9, P = .013; pMSC no-contact: 5.2 ± 0.7). After transplantation of encapsulated ICC using Ca2+ -alginate (alg) microcapsules into streptozotocin-induced diabetic and immunocompetent mice, transient normalization of glycemia was obtained up to day 7 post-transplant, whereas ICC co-encapsulated with pMSC did not improve glycemia and showed increased pericapsular fibrosis. We conclude that pMSC derived from juvenile porcine exocrine pancreas improves insulin secretion of ICC by direct cell-cell contact. For transplantation purposes, the use of pMSC to support beta-cell function will depend on the development of new anti-fibrotic polymers and/or on genetically modified pigs with lower immunogenicity.

Preoperative platelet count does not predict the occurrence of post-hepatectomy liver failure after partial hepatectomy in a retrospective monocentric cohort study.

ABSTRACT: In humans, thrombocytopenic patients have increased incidence of post-hepatectomy liver failure (PHLF), but existing evidence is heterogeneous. Our objective was to determine if preoperative platelet count or antiplatelet drugs were associated with PHLF.Patients who underwent hepatic resection in the University Hospitals of Geneva, Switzerland, from 01.12.2009 to 18.12.2018 were identified. Platelet count at day 0, postoperative days (POD) 1, 3, and 5 were retrieved. Occurrence of PHLF according to the ISGLS definition was determined. Logistic regression was performed to determine if platelet count or antiplatelet drug were predictors for PHLF.Five hundred ninety seven patients were included. Eighty patients (17.8%) had a preoperative platelet count <150 (G/l) and 24 patients (5.3%) had a platelet count <100 (G/l). Thirty five patients (5.9%) were under antiplatelet drug. Platelet count significantly decreased at POD 1 and POD 3 when compared to preoperative platelet count (182 ±â€Š71.61 (G/l) vs 212 ±â€Š85.26 (G/l), P < .0001; 162 ±â€Š68.5 (G/l) vs 212 ±â€Š85.26 (G/l), P < .0001). At POD 5, post-operative platelet count did not significantly differ from its preoperative value. Forty three patients (11.2%) suffered from PHLF. Their platelet count was not significantly different than patients without PHLF (211 ±â€Š89.7 (G/l) vs 211 ±â€Š83.5 (G/l), P = .671). One patient with PHLF had a platelet count <100 (G/l) and 5 had a count <150 (G/l). Univariate logistic regression did not identify preoperative thrombocytopenia (<100 (G/l) or <150 (G/l)), postoperative thrombocytopenia, or the presence of antiagregant drug, as predictors of PHLF. We did not identify preoperative or postoperative thrombocytopenia as predictor of PHLF in a cohort of 597 patients.

Platelet Transforming Growth Factor-ß1 Induces Liver Sinusoidal Endothelial Cells to Secrete Interleukin-6.

The roles and interactions of platelets and liver sinusoidal endothelial cells in liver regeneration are unclear, and the trigger that initiates hepatocyte proliferation is unknown. We aimed to identify the key factors released by activated platelets that induce liver sinusoidal endothelial cells to produce interleukin-6 (IL-6), a cytokine implicated in the early phase of liver regeneration. We characterized the releasate of activated platelets inducing the in vitro production of IL-6 by mouse liver sinusoidal endothelial cells and observed that the stimulating factor was a thermolabile protein. Following gel filtration, a single fraction of activated platelet releasate induced a maximal IL-6 secretion by liver sinusoidal endothelial cells (90.2 ± 13.9 versus control with buffer, 9.0 ± 0.8 pg/mL, p < 0.05). Mass spectroscopy analysis of this fraction, followed by in silico processing, resulted in a reduced list of 18 candidates. Several proteins from the list were tested, and only recombinant transforming growth factor ß1 (TGF-ß1) resulted in an increased IL-6 production up to 242.7 ± 30.5 pg/mL, which was comparable to non-fractionated platelet releasate effect. Using neutralizing anti-TGF-ß1 antibody or a TGF-ß1 receptor inhibitor, IL-6 production by liver sinusoidal endothelial cells was dramatically reduced. These results support a role of platelet TGF-ß1 ß1 in the priming phase of liver regeneration.

Platelet Interactions with Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells Lead to Hepatocyte Proliferation.

(1) Background: Platelets were postulated to constitute the trigger of liver regeneration. The aim of this study was to dissect the cellular interactions between the various liver cells involved in liver regeneration and to clarify the role of platelets. (2) Methods: Primary mouse liver sinusoidal endothelial cells (LSECs) were co-incubated with increasing numbers of resting platelets, activated platelets, or platelet releasates. Alterations in the secretion of growth factors were measured. The active fractions of platelet releasates were characterized and their effects on hepatocyte proliferation assessed. Finally, conditioned media of LSECs exposed to platelets were added to primary hepatic stellate cells (HSCs). Secretion of hepatocyte growth factor (HGF) and hepatocyte proliferation were measured. After partial hepatectomy in mice, platelet and liver sinusoidal endothelial cell (LSEC) interactions were analyzed in vivo by confocal microscopy, and interleukin-6 (IL-6) and HGF levels were determined. (3) Results: Co-incubation of increasing numbers of platelets with LSECs resulted in enhanced IL-6 secretion by LSECs. The effect was mediated by the platelet releasate, notably a thermolabile soluble factor with a molecular weight over 100 kDa. The conditioned medium of LSECs exposed to platelets did not increase proliferation of primary hepatocytes when compared to LSECs alone but stimulated hepatocyte growth factor (HGF) secretion by HSCs, which led to hepatocyte proliferation. Following partial hepatectomy, in vivo adhesion of platelets to LSECs was significantly increased when compared to sham-operated mice. Clopidogrel inhibited HGF secretion after partial hepatectomy. (4) Conclusion: Our findings indicate that platelets interact with LSECs after partial hepatectomy and activate them to release a large molecule of protein nature, which constitutes the initial trigger for liver regeneration.

Tolerogenic properties of liver macrophages in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Our understanding of non-alcoholic fatty liver disease (NAFLD) pathogenesis is improving, but there is still limited data on the function of resident liver macrophages in this context, especially when considering their contribution in dampening liver inflammation. METHODS: Liver macrophages were studied in mouse models of prolonged diet-induced liver steatohepatitis and carbon tetrachloride-induced liver injury. We assessed liver macrophages phenotype and costimulatory/inhibitory properties upon exposure to lipopolysaccharide or interleukin 4. We did phagocytosis and antigen presentation assays to investigate liver macrophages function as scavengers and immune response initiators. Using immunofluorescence staining, we further determined, in human liver tissue of patients with simple steatosis, non-alcoholic steatohepatitis and chronic hepatitis B infection, the expression of the co-inhibitory protein CD274 (Programmed-death ligand 1) and major histocompatibility complex (MHC) class II. RESULTS: Both in humans and mice, within chronically inflamed fatty livers, liver macrophages acquired immunomodulatory properties by reducing the expression of MHC class II, and by enhancing co-inhibitory signalling. Liver macrophages circumscribed endotoxin-mediated inflammatory response by upregulating anti-inflammatory genes arginase 1 and interleukin-10. While hepatic macrophages isolated from mice with normal livers were capable of achieving endotoxin tolerance, our results indicated an impairment of this protective mechanism in the presence NASH-like parenchymal abnormalities. CONCLUSIONS: Liver macrophages can achieve endotoxin tolerance, but in the chronically inflamed fatty liver, while they acquire an immunomodulatory phenotype, liver macrophages fail to dampen immune-mediated damage. Therefore, loss of tolerogenicity induced by ongoing liver insult may be a mechanism contributing to the worsening of NAFLD.

Platelets and Platelet-Derived Extracellular Vesicles in Liver Physiology and Disease.

Beyond their role in hemostasis, platelets are proposed as key mediators of several physiological and pathophysiological processes of the liver, such as liver regeneration, toxic or viral acute liver injury, liver fibrosis, and carcinogenesis. The effects of platelets on the liver involve interactions with sinusoidal endothelial cells and the release of platelet-contained molecules following platelet activation. Platelets are the major source of circulating extracellular vesicles, which are suggested to play key roles in platelet interactions with endothelial cells in several clinical disorders. In the present review, we discuss the implications of platelet-derived extracellular vesicles in physiological and pathophysiological processes of the liver.

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration.

Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non-parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.

Immunological aspects of allogeneic pancreatic islet transplantation: a comparison between mouse and human.

Pancreatic islet allotransplantation is a treatment for patients with severe forms of type 1 diabetes. As long-term graft function and survival are not yet optimal, additional studies are warranted in order to continue improving transplant outcomes. The mechanisms of islet graft loss and tolerance induction are often studied in murine diabetes models. Despite numerous islet transplantation studies successfully performed over recent years, translation from experimental mouse models to human clinical application remains elusive. This review aims at critically discussing the strengths and limitations of current mouse models of diabetes and experimental islet transplantation. In particular, we will analyze the causes leading to diabetes and compare the immunological mechanisms responsible for rejection between mouse and human. A better understanding of the experimental mouse models should facilitate translation to human clinical application.