PMC:6141714 / 42038-45459
Annnotations
MyTest
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1 diabetes mellitus is a chronic metabolic disease characterized by an insulin deficiency caused by the cellular-mediated autoimmune destruction of the β-cells of the pancreas (175). The process of destruction of pancreatic β cells, called insulitis, is a consequence of an immunological attack mediated by lymphocytes, macrophages and NK cells and leads to a permanent hyperglycemia and the need for exogenous insulin replacement (176). CD8+ T lymphocytes are the predominant type of immune cell responsible for the insulitis process, but the presence of CD4+ T lymphocytes and B lymphocytes can also be detected in the lymphocytic infiltrate in pancreatic islets (177). Furthermore, the cytokine secretion profile during the development of type 1 diabetes is typical of a Th1 pattern immune response, with the inflammatory cytokines IL-2, TNF-α, and IFN-γ being secreted in high quantities (178). The treatment of type I diabetes mellitus was conducted through the administration of hMSCs in a total of eight studies (74–80, 164). Among them, only one study (78) was conducted in humans and the other seven studies (74–77, 79, 80, 164) used mice as the experimental model. 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We propose that the levels of glycated hemoglobin is the most appropriate primary endpoint for future clinical trials as this endpoint give us an overall picture of the average serum glucose levels over a period of weeks or months. In addition, we propose that secondary endpoints such as weight gain, occurrence of episodes of hypoglycemia, systolic and diastolic blood pressure and the level of circulating lipids should be used in conjunction with the primary endpoint selected to identify the existence of multiple effects associated with hMSC administration in the pathological course of type 1 diabetes mellitus. Regarding the source of hMSCs, in four studies hMSCs were isolated from the bone marrow (77, 79, 80, 164), in three (75, 76, 78) the umbilical cord was used as the source of hMSCs and in only one study (74) hMSCs were isolated from the adipose tissue. The administration of hMSCs affected both clinical and laboratory parameters of type I diabetes. 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2_test
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1 diabetes mellitus is a chronic metabolic disease characterized by an insulin deficiency caused by the cellular-mediated autoimmune destruction of the β-cells of the pancreas (175). The process of destruction of pancreatic β cells, called insulitis, is a consequence of an immunological attack mediated by lymphocytes, macrophages and NK cells and leads to a permanent hyperglycemia and the need for exogenous insulin replacement (176). CD8+ T lymphocytes are the predominant type of immune cell responsible for the insulitis process, but the presence of CD4+ T lymphocytes and B lymphocytes can also be detected in the lymphocytic infiltrate in pancreatic islets (177). Furthermore, the cytokine secretion profile during the development of type 1 diabetes is typical of a Th1 pattern immune response, with the inflammatory cytokines IL-2, TNF-α, and IFN-γ being secreted in high quantities (178). The treatment of type I diabetes mellitus was conducted through the administration of hMSCs in a total of eight studies (74–80, 164). Among them, only one study (78) was conducted in humans and the other seven studies (74–77, 79, 80, 164) used mice as the experimental model. Among the studies conducted in mice, the fasting and post-prandial plasma glucose level, the C-peptide level, the rate of change in body weight, the serum insulin level, the total number of islets and the ratio of β and α cells per islet were the outcomes used by most animal studies selected in this systematic review to assess the potential of hMSCs administration for the treatment of type 1 diabetes mellitus. In the human clinical trial selected, the primary study endpoints used were: feasibility of the stem cell therapy; safety of the therapy through 24 months post-treatment; and the preliminary evaluation of the efficacy of the therapy for improving β cell function through 24 weeks. The secondary study endpoint used was the evidence of the efficacy of the therapy in modulating autoimmunity. We propose that the levels of glycated hemoglobin is the most appropriate primary endpoint for future clinical trials as this endpoint give us an overall picture of the average serum glucose levels over a period of weeks or months. In addition, we propose that secondary endpoints such as weight gain, occurrence of episodes of hypoglycemia, systolic and diastolic blood pressure and the level of circulating lipids should be used in conjunction with the primary endpoint selected to identify the existence of multiple effects associated with hMSC administration in the pathological course of type 1 diabetes mellitus. Regarding the source of hMSCs, in four studies hMSCs were isolated from the bone marrow (77, 79, 80, 164), in three (75, 76, 78) the umbilical cord was used as the source of hMSCs and in only one study (74) hMSCs were isolated from the adipose tissue. The administration of hMSCs affected both clinical and laboratory parameters of type I diabetes. In most of the studies selected, the administration of hMSCs resulted in a decrease in the blood glucose level (74–80) and in an increase in both the survival rates (75) and in the insulin level in the blood (75, 77, 79, 80). Furthermore, treatment with hMSCs delayed the onset of the disease (76, 164), reduced the weight loss resulting from the disease (74), inhibited insulitis in islets (75, 76, 164) and increased pancreatic islet number and function (74–78, 80)."}