Reprogramming gut and pancreas endocrine cells to treat diabetes (original) (raw)
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Re-engineering islet cell transplantation
Pharmacological research : the official journal of the Italian Pharmacological Society, 2015
We are living exciting times in the field of beta cell replacement therapies for the treatment of diabetes. While steady progress has been recorded thus far in clinical islet transplantation, novel approaches are needed to make cell-based therapies more reproducible and leading to long-lasting success. The multiple facets of diabetes impose the need for a transdisciplinary approach to attain this goal, by targeting immunity, promoting engraftment and sustained functional potency. We discuss herein the emerging technologies applied to beta cell replacement therapies.
Bioengineered Islet Cell Transplantation
Current Transplantation Reports, 2021
Purpose of Review β cell replacement via whole pancreas or islet transplantation has greatly evolved for the cure of type 1 diabetes. Both these strategies are however still affected by several limitations. Pancreas bioengineering holds the potential to overcome these hurdles aiming to repair and regenerate β cell compartment. In this review, we detail the state-of-the-art and recent progress in the bioengineering field applied to diabetes research. Recent Findings The primary target of pancreatic bioengineering is to manufacture a construct supporting insulin activity in vivo. Scaffold-base technique, 3D bioprinting, macro-devices, insulin-secreting organoids, and pancreas-on-chip represent the most promising technologies for pancreatic bioengineering. Summary There are several factors affecting the clinical application of these technologies, and studies reported so far are encouraging but need to be optimized. Nevertheless pancreas bioengineering is evolving very quickly and its c...
Immune Protection of Stem Cell-Derived Islet Cell Therapy for Treating Diabetes
Frontiers in Endocrinology, 2021
Insulin injection is currently the main therapy for type 1 diabetes (T1D) or late stage of severe type 2 diabetes (T2D). Human pancreatic islet transplantation confers a significant improvement in glycemic control and prevents life-threatening severe hypoglycemia in T1D patients. However, the shortage of cadaveric human islets limits their therapeutic potential. In addition, chronic immunosuppression, which is required to avoid rejection of transplanted islets, is associated with severe complications, such as an increased risk of malignancies and infections. Thus, there is a significant need for novel approaches to the large-scale generation of functional human islets protected from autoimmune rejection in order to ensure durable graft acceptance without immunosuppression. An important step in addressing this need is to strengthen our understanding of transplant immune tolerance mechanisms for both graft rejection and autoimmune rejection. Engineering of functional human pancreatic ...
The Journal of Immunology, 2007
We have previously shown that the development of type 1 diabetes (T1D) can be prevented in nonobese diabetic (NOD) mice by reconstitution with autologous hemopoietic stem cells retrovirally transduced with viruses encoding MHC class II I-A β-chain molecules associated with protection from the disease. In this study we examined whether a blockade of the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway, a major pathway known to control diabetes occurrence, could precipitate T1D in young NOD mice following reconstitution with autologous bone marrow retrovirally transduced with viruses encoding protective MHC class II I-A β-chain molecules. In addition, we examined whether the expression of protective MHC class II alleles in hemopoietic cells could be used to prevent the recurrence of diabetes in mice with pre-existing disease following islet transplantation. Protection from the occurrence of T1D diabetes in young NOD mice by the expression of protective MHC class II ...
Insulin gene transfer enhances the function of human islet grafts
Diabetologia, 2003
Recent success in islet transplantation renews the hope for the complete cure of patients afflicted with Type 1 diabetes. However, in the Edmonton series, two to four pancreas donors were required to obtain a sufficient islet mass to reverse the diabetes of each patient. In view of the donor shortage, this represents a major obstacle preventing greater application of islet transplantation to diabetic patients. We hypothesised that increasing the expression of the insulin gene in transplanted islets would augment their capacity for insulin production, thereby allowing reversal of diabetes with a reduced islet mass. We used a replication defective adenovirus to deliver the human proinsulin gene (Ad-Ins) to isolated human islets. The function of Ad-Ins-transduced human islets was compared to islets transduced with a control vector (Ad-lacz). Ad-Ins-transduced islets produced two to three times more insulin than normal islets or those infected with Ad-lacz, as assessed by in vitro perif...