Cell therapy for type 1 diabetes

Muir, Kenneth; Lima, Maria João; Docherty, Hilary M.; Docherty, Kevin

doi:10.1093/qjmed/hcu025

Cited by 21 publications

(21 citation statements)

References 38 publications

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“…Clinical islet transplantation has been shown to be a viable option for treatment of type 1 diabetes . Xenotransplantation of porcine islets is a promising alternative to bridge the gap between available human cells and the needs of patients with diabetes .…”

Section: Introductionmentioning

confidence: 99%

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

Nie

Yang

et al. 2018

Xenotransplantation

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Section: Introductionmentioning

confidence: 99%

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

Nie

Yang

et al. 2018

Xenotransplantation

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“…A small number of pluripotent cell lines have been used to form islets for transplantation, in which these cells would be generated, maintained, and differentiated under GMP-grade condition and expected to expand up to 1 million islets for a single transplantation [12].…”

Section: Differentiation Of Pluripotent Stem Cells Into β-Cellsmentioning

confidence: 99%

“…Currently, it is still not possible to turn stem cells further into 100% functional β-cells, however, in a study involving streptozotocin (STZ)-induced diabetic mice, the cells that were implanted under kidney capsule or epididymal fat pad, were capable of secreting C-peptide as a response to glucose after 12 weeks. It is important to note that C-peptide at the normal range indicates good response to tolerance test, which means that even a small amount of insulin production is beneficial for glycemic control [12].…”

Section: Differentiation Of Pluripotent Stem Cells Into β-Cellsmentioning

confidence: 99%

“…ARRIVE for in vivo experimental studies The use of ARRIVE guideline is intended to improve reporting of in vivo studies [15]. ARRIVE consisted of 20 components that have been developed using CONSORT as the foundation.15 Criteria 1,2,3,4,6,7,8,9,10,11,12,14,15,16,17 correspond to the internal validity, criteria 5, 18, 19, 20 correspond to external validity, while criteria 13 correspond to statistical analysis of the included studies. The criterias were scored using predefined gradings [15]:  0 = inaccurate/not concise/clearly insufficient/not clear/no  1= accurate/concise/possibly accurate/possibly sufficient /clear/ adequate/yes  2 = clearly accurate/clearly sufficient/clearly adequate/yes in which each component has the maximum score of 2 and minimum amount of 0 [15]0.…”

Section: Quality Assessmentmentioning

confidence: 99%

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A Comparison Between Islet And Stem Cell Transplantation For Treatment Of Type 1 Diabetes Mellitus: A Systematic Review

2016

IJDMD

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Introduction:The incidence of type 1 Diabetes Mellitus (T1DM) has been increasing rapidly worldwide in the past decade. The current standard treatment is exogenous insulin therapy, however, this procedure is highly associated with poor glycemic control that may lead to life-threatening hypoglycemic episodes. Cellular-based therapy for T1DM has been recently developed, making it pertinent to compare the effectiveness between two most anticipated breakthroughs: islet cell and stem cell transplantation, in order to determine which procedure is more effective.Methods: A comprehensive digital literature search was performed using PubMed and Ovid Medline for primary research studies published between Jan 2000 -Nov 2015. Relevant cohort, case-control, case series, and in vivo studies were included. The abstracts and full text of the retrieved articles were scanned for potential studies that fulfilled the inclusion criterias. The quality assessment of studies were conducted using ARRIVE, NOS, and MINORS. Results:Nineteen primary research studies met the inclusion criterias and were assessed for the review. Eleven out of 19, were considered as high-quality, while the rest were moderate-quality. The studies generally reported the insulin independence, graft functionality, and glycemic control. The insulin-independent period for islet cell tranplantation was proven to be longer compared to stem cell transplantation with better glycemic control. Stem cells were successfully differentiated into glucoseresponsive insulin-producing cells, that also released glucagon and somatostatin.Discussion: The majority of the included studies were using the same outcome measures which allow a more comprehensive comparison to be conducted. Based on the assessment, islet cell transplantation is currently better. This treatment was found to lead to significant improvements in insulin independence and glycemic control observed through insulin-free period, HbA1c, blood glucose, and C-peptide serum measurement. On the other hand, certain challenges -such as donor shortage and poor engraftment -hinders the widespread application of the treatment. Therefore, stem cell transplantation is thought to possibly be replacing islet cell transplantation in the future. Stem cells had successfully been differentiated into β-like cells that were not only producing insulin, but also glucagon and somatostatin, as well as acting in glucose-stimulated manner, imitating the physiologic mechanism of β-cells. Conclusion:It is conclusive that islet stem cell transplantation was proven to perform relatively better in terms of insulin independence and glycemic control compared to stem cell transplantation for treating T1DM. Both cellular-based treatments provided relatively better glycemic control compared to the current standard treatment, exogenous insulin therapy. All the studies have reported that both treatments lead to substantial improveent between pre-and post-transplantation periods. Stem cell transplantation was also proven to have unlimited potentials to be...

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“…It has been reported that mouse ESCs can differentiate into neural stem cells, pancreatic β cells, hematopoietic stem cells, cardiomyocytes, and osteoblasts after induction in vitro. ESCs can be used for tissue repair and functional replacement therapy, which may provide a new strategy for future treatment of some irreversible diseases such as heart failure, hereditary diseases, diabetes, and neuronal degeneration [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Pdx1 expression up-regulated by Tet-on system induces the mouse embryonic stem cells to pancreatic-like cells through Notch pathway

Lai

Xia

et al. 2020

Preprint

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Background The specific precursor cells derived from embryonic stem cells (ESCs) after induced differentiation offers great potential for repairing damaged pancreas. Therefore, it is of crucial importance to know whether pancreatic precursor cells with Pdx1+ could be induced to differentiate into pancreatic-like cells in vitro as well as the probable mechanism underlying. Methods In this study, mouse ESCs (ES-E14TG2a) were divided into the blank control group (ESC), the blank vector group (Pdx1− ESC), and the Pdx1 lentiviral vector group (Pdx1+ ESC). We constructed lentiviral vectors with overexpressed Pdx1 in Tet-on system and screened the stably transfected cell lines after transfection. CXCR4+ (C-X-C chemokine receptor type 4) DE cells of the three groups were seeded (day zero [d0]) after being sorted with immune beads, and expression of Pdx1 was induced on the second day (d1). Then, markers for the differentiation of Pdx1+ pancreatic precursor cells and molecules in the Notch pathway were detected at d3, d7, d10, and, d14. Results We found that expressions of Ptf1a, CK19, and amylase increased at d3 and d7, Neuro D1 increased at d10 and d14, Pax6 and insulin increased at d14, as well as Notch1, Notch2, Hes1, and Hes5 increased at d3 and thereafter declined at d14 in the Pdx1+ ESC group. These expressions were significantly higher than those in the ESC group and Pdx1− ESC group, but no marked differences were observed between the ESC group and Pdx1− ESC group. Conclusions Our study indicates that Pdx1+ pancreatic precursor cells can differentiate into pancreatic-like cells in which the Notch pathway plays important roles.

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Cell therapy for type 1 diabetes

Cited by 21 publications

References 38 publications

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

A Comparison Between Islet And Stem Cell Transplantation For Treatment Of Type 1 Diabetes Mellitus: A Systematic Review

Pdx1 expression up-regulated by Tet-on system induces the mouse embryonic stem cells to pancreatic-like cells through Notch pathway

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