Early immunotherapy using autologous adult stem cells reversed the effect of anti-pancreatic islets in recently diagnosed type 1 diabetes mellitus: Preliminary results

Abstract Background: Mesenchymal stem cells (MSCs) shows significant therapeutic effects in type 1 diabetes mellitus (T1DM) as they could regulate the inflammatory processes. However, little is known about the process of MSCs immunosuppression in T1DM. In this study, we investigated the effects of wild type p53-induce phosphatase 1 (Wip1) on regulating MSCs immunosuppressive capacities in T1DM mice.Methods: Primary wild type (Wip1+/+) MSCs and Wip1 knockout (Wip1−/−) MSCs were cultured in vitro. T1DM mouse model was induced with streptozotocin and then was treated with Wip1+/+ MSCs (5 × 105) or Wip1−/− MSCs (5 × 105) by tail vein injection. The general physiological states of T1DM mice were measured every week. Moreover, the pathological changes in the pancreatic tissue were observed. Enzyme-linked immunosorbent assay (ELISA) and flow cytometry were used to detect the expressions of inflammatory cytokines in mice.Results: Wip1 −/− MSCs had lower therapeutic effects in T1DM mice. Moreover, we screened and confirmed bone marrow stromal cell antigen2 (BST2) gene that showed the target gene for Wip1 through gene chips, quantitative polymerase chain reaction and Western blot. Wip1−/− MSCs exhibited lower immunosuppressive capacity, as evidenced by enhanced expression of BST2, with concurrent increased expression of interferon-α (IFN-α). In vivo distribution analysis results indicated that Wip1−/− MSCs homed to the damaged pancreatic tissue. Wip1−/− MSCs influenced the expression of immune factors by remarkably increasing the expression of tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A), IFN-α, IFN-β, and IFN-γ and decreasing the expression of IL-4 and IL-10.Conclusions: Wip1 affects MSCs immunomodulation by regulating the expression of IFN-α/BST2. These findings suggest that Wip1 is required to regulate the therapeutic effects of MSCs on T1DM treatment, indicating a novel role of Wip1 in immunoregulation.

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Autologous and allogeneic transplantation of adipose derived stem cells have similar efficacy for type 1 diabetes mellitus therapy in mouse models

Progress in Stem Cell ◽

10.15419/psc.v3i04.142 ◽

2016 ◽

Vol 3 (04) ◽

pp. 129

Author(s):

Anh Nguyen-Tu Bui ◽

Oanh Thi-Kieu Nguyen ◽

Cong Le-Thanh Nguyen ◽

Loan Thi-Tung Dang ◽

Dung Phuong Nguyen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Stem Cells ◽

Type 1 Diabetes ◽

Blood Glucose ◽

Mortality Rate ◽

Pancreatic Islets ◽

Insulin Level ◽

Adipose Derived Stem Cells ◽

Glucose Levels

Introduction: Type 1 diabetes mellitus (T1D) disease is caused by lesions or dysfunction of beta cells of pancreatic islets, causing less insulin to be secreted into the blood and thereby increasing glucose levels in the blood. In this study, we evaluated and compared the efficiency of treatment for T1D using autograft and allograft adipose-derived stem cells (ADSCs). Methods: ADSCs were collected from the belly of mice before they were injected using a single dose of streptozotocin (100 mg/kg) to induce T1D. T1D mice were intravenously injected with a dose of 2x106 ADSCs into the tail vein. Therapeutic efficacy was assessed by survival rate, blood glucose levels, serum insulin levels, histology and immunohistochemistry of pancreatic islets. Results: The results showed that both autograft and allograft transplantation of ADSCs demonstrated similarities in mortality rate, blood glucose level, blood insulin level, quantity and size of pancreatic islets. Both transplantations significantly improved T1D mice, which showed a decrease in mortality rate as well as blood glucose level, and increases in blood insulin level, quantity and size of pancreatic islets. Conclusion: The similar results suggest that both autologous and allogeneic transplantations of ADSCs are promising therapy for T1D treatment.

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ID: 1079 Improved glucose homeostasis effect of conditioned media from adipose-derived stem cells in type 1 diabetic mice

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.353 ◽

2017 ◽

Vol 4 (S) ◽

pp. 165

Author(s):

Anh Nguyen Tu Bui ◽

Cong Le Thanh Nguyen ◽

Ngoc Kim Phan ◽

Loan Thi-Tung Dang

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Stem Cell ◽

Blood Glucose ◽

Blood Glucose Level ◽

Type 1 Diabetes Mellitus ◽

Pancreatic Islets ◽

Conditioned Medium ◽

Diabetic Mice

Background: Many studies suggested adipose derived stem cell (ASC) transplantation as a new approach to control hyperglycemia in type 1 diabetes mellitus. It is proposed that the effects of these cells could be not only based on the direct cell-cell interaction but also the secretion of cytokines. This study aimed to demonstrate the effect of adipose stem cell-derived conditioned medium (CM) on the treatment of STZ-induced diabetic mice. Methods: CM was obtained from 24-hours-cultured medium of ASCs and centrifuged to remove the debris. Type 1 diabetic mice were intraperitoneally injected CM for 30 consecutive days. Therapeutic efficacy of CM was assessed by survival rate, blood glucose level, serum insulin level, histological structure of pancreatic islets. Results: The results showed that CM treatment could decrease mortality rate (from 33,33% to 0%) as well as blood glucose level (from 425,667±65,753 mg/dl to 203,500 mg ±20,350 mg/dl) and enhance insulin secretion, improve size and function of pancreatic islets of diabetic mice. Conclusion: Conditioned medium maybe a promising therapy for type 1 diabetes mellitus.

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Exosome Degeneration in Mesenchymal Stem Cells Derived from Patients with Type 1 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms222010906 ◽

2021 ◽

Vol 22 (20) ◽

pp. 10906

Author(s):

Michiko Horiguchi ◽

Yuko Okada ◽

Yuya Turudome ◽

Kentaro Ushijima

Keyword(s):

Diabetes Mellitus ◽

Stem Cells ◽

Type 1 Diabetes ◽

Mesenchymal Stem Cells ◽

Type 1 Diabetes Mellitus ◽

Adipose Derived Stem Cells ◽

Β Cells ◽

Pancreatic Β Cells ◽

Healthy Humans

Type 1 diabetes mellitus is characterized by the destruction of pancreatic β-cells and requires the regeneration of these destroyed pancreatic β-cells for radical treatment. The degeneration of organelles in stem cells compromises stem cell quality; however, organelles in the mesenchymal stem cells of patients with type 1 diabetes mellitus have not been characterized previously. In this study, we use transmission electron microscopy to evaluate the degeneration of organelles in adipose-derived stem cells of patients with type 1 diabetes mellitus (T1DM ADSCs). Compared to adipose-derived stem cells from healthy humans, T1DM ADSCs degenerate differently, characterized by prominent enlarged spherical vesicles. The exosomes of T1DM ADSCs are found to be enlarged, reduced in number, and increased in the percentage of those positive for tetraspanin CD9. The findings of this study provide insight into the characteristics of stem cells in patients with type 1 diabetes mellitus.

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