1,721,154 research outputs found
The Last Mile in Beta-Cell Replacement Therapy for Type 1 Diabetes: Time to Grow Up
Full text linkBeta cell replacement therapy for type 1 diabetes (T1D) is undergoing a transformative shift, driven by advances in stem cell biology, gene editing, and tissue engineering. While islet transplantation has demonstrated proof-of-concept success in restoring endogenous insulin production, its clinical impact remains limited by donor scarcity, immune rejection, and procedural complexities. The emergence of stem cell-derived beta-like cells represents a paradigm shift, with initial clinical trials showing promising insulin secretion in vivo. However, translating these breakthroughs into scalable, widely accessible treatments poses significant challenges. Drawing parallels to space exploration, this paper argues that while scientific feasibility has been demonstrated, true accessibility remains elusive. Without a strategic shift, beta cell therapy risks becoming an elite intervention, restricted by cost and infrastructure. Lessons from gene and cell therapies for rare diseases highlight the dangers of unsustainable pricing and limited market viability. To bridge the "last mile" a Quality by Design approach is proposed, emphasizing scalability, ease of use, and economic feasibility from the outset. By emphasizing practical implementation over academic achievements, corporate interests, market economics, or patent constraints, beta cell therapy can progress from proof-of-concept to a viable, widely accessible treatment
Mesenchymal stem cells as feeder cells for pancreatic islet transplants
No full textAllogeneic islet transplantation serves as a source of insulin-secreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients. Copyright © by Lab & Life Press/SBDR
COVID-19 and islet transplantation: different twins
No full textFor those who work in the field of islet transplantation, the micro vascular COVID-19 lung vessels obstructive thrombo-inflammatory syndrome (recently referred to as MicroCLOTS) is familiar, as one cannot fail to recognize the presence of similarities with the instant blood mediated inflammatory reaction (IBMIR) occurring in the liver hours and days after islet infusion. Evidences in both MicroCLOTS and IBMIR suggest the involvement of the coagulation cascade and complement system activation, and proinflammatory chemokines/cytokines release. Identification and targeting of pathway(s) playing a role as “master regulator(s)” in the post-islet transplant detrimental inflammatory events could be potentially useful to suggest innovative COVID-19 treatments and vice versa. All the scientific organizations across the world are fighting the COVID-19 pandemic. Islet transplantation, and more generally the transplantation scientific community, could contribute suggesting strategies for innovative approaches. At the same time, in the near future, clinical trials in COVID-19 patients will produce an enormous quantity of clinical and translational data on the control of inflammation, and complement/microthrombosis activation. These data will represent a legacy to be transformed into innovation in the transplant field. It will be our contribution to change a dramatic event into advancement for the transplant field, and ultimately for our patients
Islet autotransplantation in intraductal papillary mucinous neoplasm: A “Pole Pole” (slowly, slowly) path toward careful expansion of indications
No full textImmune Evasive Stem Cell Islets
No full textType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of insulin-secreting ß cells by the immune system (American Diabetes, A., Diabetes Care 32 Suppl 1:S62-67, 2009). It is characterized by fasting or post prandial elevated blood glucose levels and islet-associated autoantibodies (American Diabetes, A., Diabetes Care 32 Suppl 1:S62-67, 2009). While the administration of exogenous insulin remains the standard treatment for T1D patients, it does not restore pancreatic functionality and can result in hypoglycemia and long-term vascular complications (Fotino et al., Pharmacol Res 98:76-85, 2015; Latres et al., Cell Metab 29:545-563, 2019; Wang et al., Adv Sci (Weinh) 8, 2021). To date, the most effective approach to achieving normoglycemia and metabolic control in T1D patients is the transplantation of pancreatic islets (Hering et al., Diabetes Care 39:1230-1240, 2016). However, the shortage of cadaveric donors as well as the risk of immune rejection and the need for immunosuppressive therapies pose significant challenges. The production of differentiated ß cells from induced pluripotent stem cells (iPSC) represents a promising option to overcome these limitations. Indeed, iPSC are reprogrammed from adult somatic cells, providing a virtually unlimited source of cells for cell therapy (Millman et al., Nat Commun 7:11463, 2016). Moreover, the use of autologous patient-derived iPSC for ß cell transplantation does not elicit an immune response in the recipient (de Almeida et al., Nat Commun 5:3903, 2014; Sordi et al., Curr Diab Rep 17:68, 2017). However, the feasibility of a personalized approach, by which iPSC are generated and differentiated from individual T1D patients, is hampered by high costs and time-consuming procedures (Gornalusse et al., Nat Biotechnol 35:765-772, 2017; Sordi et al., Curr Diab Rep 17:68, 2017; Wang et al., Stem Cells Transl Med 4:1234-1245, 2015). Therefore, the identification of a strategy for ß cell replacement employing allogeneic iPSC or embryonic stem cells (ESC) and successfully escaping immune rejection is of the highest interest
Enhancing Beta Cell Replacement Therapies: Exploring Calcineurin Inhibitor-Sparing Immunosuppressive Regimens
Full text linkAssisted reproductive technology and the risk of fetal congenital heart disease: insights from a tertiary-care referral center
Full text linkPurpose: To investigate whether congenital heart diseases exhibit higher rates in pregnancies achieved through assisted reproductive technology (ART) compared to natural conception. Methods: In this retrospective cohort study, multinomial logistic regression was employed to analyze the relationship between categories of congenital heart diseases and three conception groups (IVF, ICSI, and natural pregnancies). The main outcome measures are risks of congenital heart disease categories in IVF and ICSI groups using the natural group as reference. We selected fetuses referred for fetal echocardiography to IRCCS Policlinico Sant’Orsola, Bologna, between January 2005 and November 2023, diagnosed with congenital heart diseases. Results: We categorized the congenital heart diseases into six groups based on anatomical and embryological criteria. The estimated risk of left ventricular outflow tract, valvular, conotruncal, and atrioventricular septal defects was lower in the IVF group compared to natural conception. The estimated risk of valvular and atrioventricular septal defects was lower in the ICSI group vs natural. Conversely, the risk for right heart anomalies was higher both in the IVF and ICSI groups compared to natural conception. Heart rhythm diseases were more frequent in IVF pregnancies. When comparing ART methods, valvular defects, conotruncal defects, and right heart anomalies were more frequently observed in the ICSI group, while atrioventricular septal defects were more common in the IVF group. Conclusion: Significant differences were found in the occurrence of congenital heart diseases in pregnancies conceived through IVF and ICSI, versus those conceived naturally, underscoring the importance of further studying the underlying mechanisms of these associations
From pattern recognition receptor to regulator of homeostasis: The double-faced macrophaqe mannose receptor
No full textThe mannose receptor (MR) is an endocytic and phagocytic receptor belonging to the C-type lectin superfamily. A number of functions have been ascribed to this receptor, which is involved in innate and adaptive immune responses. The MR binds carbohydrate moieties on several pathogens, such as bacteria, fungi, parasites, and viruses, and, therefore, is considered a pattern recognition receptor (PRR). In addition, MR binds endogenous molecules and was originally described as a membrane-associated component binding lysosomal glycosidases in alveolar macrophages. Since its identification more than 25 years ago, many other endogenous ligands were described, including hormones, enzymes, cell membranes, extracellular matrix components, and normal as well as tumoral mucins. The MR is preferentially expressed on immune cells of myeloid lineage, especially subsets of dendritic cells (DC) and tissue macrophages. In addition to immune cells, specialized endothelial cells are also MR-positive. Increasing evidence shows that the MR is involved in the silent clearance of inflammatory molecules. In this review, we discuss current knowledge about the receptor and show that endogenous ligands activate an anti-inflammatory and tolerogenic program in DC and macrophages, thus reinforcing the hypothesis that the MR has an important role in the maintenance of homeostasis
Total pancreatectomy sequelae and quality of life: results of islet autotransplantation as a possible mitigation strategy
No full textTotal pancreatectomy (TP) is a procedure weighed down not only by postoperative morbidity and mortality but also by long-term effects as a consequence of endocrine and exocrine pancreatic insufficiency. While the latter is now managed quite effectively with pancreatic enzyme replacement therapy, the former remains a challenge. The diabetes resulting after TP, with the complete loss of endogenous insulin and contraregulatory hormones, is characterized by important glycemic variations and is, therefore, frequently referred to as “brittle diabetes”. One method to reduce the impact of brittle diabetes in patients undergoing TP is the re-infusion of autologous pancreatic islets isolated from the resected pancreas. Indications to islet autotransplantation (IAT), originally described for patients undergoing TP for chronic pancreatitis, have since been extended to selected patients with other benign and malignant diseases of pancreas. This review recaps on the literature regarding long-term postoperative complications, their impact on quality of life after TP and the role of IAT
Pig Xenotransplantation in Beta Cell Replacement: Addressing Challenges and Harnessing Potential for Type 1 Diabetes Therapy
Full text linkThis opinion paper evaluates the potential of porcine islets as a promising alternative in beta cell replacement therapy for Type 1 Diabetes (T1D), juxtaposed with the current limitations of human donor islets. It analyzes the compatibility of pig islets with human glucose metabolism, their prospects as a limitless and high-quality source of beta cells, and the unique immunogenic challenges they present in xenotransplantation. Additionally, the paper discusses the regulatory and ethical considerations pertinent to the use of porcine islets. By synthesizing current research and expert perspectives, the paper highlights both the opportunities and significant barriers that need addressing to advance pig islets as a viable therapeutic option. The findings advocate for a balanced and forward-looking approach to the integration of pig islets in T1D treatment, underscoring the need for continued research and dialogue in this evolving field
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