Overcoming the Limitations of Stem Cell-Derived Beta Cells

Karimova, Mariana V.; Gvazava, I. G.; Vorotelyak, E. A.

doi:10.3390/biom12060810

Cited by 10 publications

(4 citation statements)

References 112 publications

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“…It has been found that patients with diabetes mellitus and myocardial infarction have an increase in the level of endogenous malondialdehyde (MDA) and diene conjugates in the blood serum. The results obtained indicate the presence of oxidative stress in diabetes mellitus and myocardial infarction [6,7,8].…”

Section: Introductionmentioning

confidence: 70%

Effects of Transplantation of MSCS and Pancreatic Beta Cells on Metabolic Parameters of Blood Plasma in Rats With Myocardial Infarction With Underlying Diabetes Mellitus

Mykhaylichenko¹,

Pilipchuk²,

Bondarenko³

et al. 2022

ArveMED

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The purpose of this work was to study the role of transplantation of mesenchymal stem cells (MSCs) and pancreatic beta cells (BCs) in metabolism of rats with diabetes mellitus (DM) and myocardial infarction (MI). The animals formed 4 groups, 24 in each: control group - healthy Wistar-Kyoto animals, which served as the norm for the studied parameters; group 1 in which animals with diabetes mellitus had a myocardial infarction simulated by ligation of the left gastric artery after the first branch; group 2 – rats with the model of MI and DM which, on the day 2 after the modeling, had transplantation of rat mesenchymal stem cells taken from the bone marrow of tubular bones; group 3 – rats with DM+MI model which received transplantation of MSCs and rat pancreatic BCs on the day 2 after the modeling. We dynamically studied the activity of aspartate aminotransferase enzymes, creatine kinase-MB, blood plasma lactate dehydrogenase, and haptoglobin and ceruloplasmin proteins. The study revealed that cardiomyoplasty with MSCs caused a positive metabolic effect. MSC transplantation is accompanied by a decrease in the activity of ADA and LDH enzymes in the damaged myocardium, which indirectly indicates an increase in the energy balance of energy-forming substrates and a decrease in the degree of myocardial ischemia. A decrease in the accumulation of lipid peroxidation products and the tension of the non-enzymatic antioxidant protection is a good prognostic criterion for the restoration of the functional activity of the damaged myocardium. The transplantation of a mixed culture of MSCs and pancreatic BCs makes it possible to fully compensate for carbohydrate metabolism, to achieve the best performance in the studied groups in terms of lipid peroxidation regulation and activation of the antioxidant system.

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Section: Introductionmentioning

confidence: 70%

Effects of Transplantation of MSCS and Pancreatic Beta Cells on Metabolic Parameters of Blood Plasma in Rats With Myocardial Infarction With Underlying Diabetes Mellitus

Mykhaylichenko¹,

Pilipchuk²,

Bondarenko³

et al. 2022

ArveMED

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“…modified the nutrients in the medium used for in vitro differentiation to further enhance generating functional SC-β-cells in vitro ( 52 ), and could also induce SC-β-cells by simulating the 3D culture system of human pancreatic development ( 53 ). In addition, Isaura ( 54 ) and Mariana ( 55 ) et al. recently updated and detailed the recent progress in using ESCs/iPSCs derived islet β-cells in vitro .…”

Section: β-Cell Replacement Options: Stem Cells and Porcine Isletsmentioning

confidence: 99%

Pancreatic islet transplantation: current advances and challenges

Wang,

Huang,

Liu

et al. 2024

Front. Immunol.

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Diabetes is a prevalent chronic disease that traditionally requires severe reliance on medication for treatment. Oral medication and exogenous insulin can only temporarily maintain blood glucose levels and do not cure the disease. Most patients need life-long injections of exogenous insulin. In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin and avoid complications.Long-term follow-up results from recent reports on islet transplantation suggest that they provide significant therapeutic benefit although patients still require immunotherapy, suggesting the importance of future transplantation strategies. Although organ shortage remains the primary obstacle for the development of islet transplantation, new sources of islet cells, such as stem cells and porcine islet cells, have been proposed, and are gradually being incorporated into clinical research. Further research on new transplantation sites, such as the subcutaneous space and mesenteric fat, may eventually replace the traditional portal vein intra-islet cell infusion. Additionally, the immunological rejection reaction in islet transplantation will be resolved through the combined application of immunosuppressant agents, islet encapsulation technology, and the most promising mesenchymal stem cells/regulatory T cell and islet cell combined transplantation cell therapy. This review summarizes the progress achieved in islet transplantation, and discusses the research progress and potential solutions to the challenges faced.

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“…In addition, the overall function of islet organoids is also defective compared to that of natural islets, such as the lack of an intact neurohumoral regulatory system and a synchronized, stable, and rapid insulin release from numerous β-cells based on it [ 124 ]. The defects in the overall function of islet organoids may also be associated with factors like the vascularization levels, the composition and arrangement of EC cells, and the heterogeneity of β-cells.…”

Section: Challenges In Construction and Application Of Islet Organoidmentioning

confidence: 99%

Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus

Li,

Xu,

Chen

et al. 2024

Stem Cell Res Ther

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Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body’s in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.

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Overcoming the Limitations of Stem Cell-Derived Beta Cells

Cited by 10 publications

References 112 publications

Effects of Transplantation of MSCS and Pancreatic Beta Cells on Metabolic Parameters of Blood Plasma in Rats With Myocardial Infarction With Underlying Diabetes Mellitus

Effects of Transplantation of MSCS and Pancreatic Beta Cells on Metabolic Parameters of Blood Plasma in Rats With Myocardial Infarction With Underlying Diabetes Mellitus

Pancreatic islet transplantation: current advances and challenges

Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus

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