scholarly journals Development of a Bioartificial Vascular Pancreas

2021 ◽  
Vol 12 ◽  
pp. 204173142110277
Author(s):  
Edward X Han ◽  
Juan Wang ◽  
Mehmet Kural ◽  
Bo Jiang ◽  
Katherine L Leiby ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Islets ◽  
Vascular Graft ◽  
Term Treatment ◽  
Diffusion Limitations ◽  
Human Scale ◽  
Arterial Blood ◽  
Long Term Treatment

Transplantation of pancreatic islets has been shown to be effective, in some patients, for the long-term treatment of type 1 diabetes. However, transplantation of islets into either the portal vein or the subcutaneous space can be limited by insufficient oxygen transfer, leading to islet loss. Furthermore, oxygen diffusion limitations can be magnified when islet numbers are increased dramatically, as in translating from rodent studies to human-scale treatments. To address these limitations, an islet transplantation approach using an acellular vascular graft as a vascular scaffold has been developed, termed the BioVascular Pancreas (BVP). To create the BVP, islets are seeded as an outer coating on the surface of an acellular vascular graft, using fibrin as a hydrogel carrier. The BVP can then be anastomosed as an arterial (or arteriovenous) graft, which allows fully oxygenated arterial blood with a pO2 of roughly 100 mmHg to flow through the graft lumen and thereby supply oxygen to the islets. In silico simulations and in vitro bioreactor experiments show that the BVP design provides adequate survivability for islets and helps avoid islet hypoxia. When implanted as end-to-end abdominal aorta grafts in nude rats, BVPs were able to restore near-normoglycemia durably for 90 days and developed robust microvascular infiltration from the host. Furthermore, pilot implantations in pigs were performed, which demonstrated the scalability of the technology. Given the potential benefits provided by the BVP, this tissue design may eventually serve as a solution for transplantation of pancreatic islets to treat or cure type 1 diabetes.

Islet Encapsulation: A Long-Term Treatment for Type 1 Diabetes

2019 ◽  
Author(s):  
Brenden N. Moeun ◽  
Si Da Ling ◽  
Marco Gasparrini ◽  
Alissa K. Rutman ◽  
Sarita Negi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Term Treatment ◽  
Islet Encapsulation ◽  
Long Term Treatment

The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin

2016 ◽  
Vol 175 (8) ◽  
pp. 1123-1128
Author(s):  
Monica Del Rizzo ◽  
Alfonso Galderisi ◽  
Andrea Celato ◽  
Francesca Furlan ◽  
Laura Giordano ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Term Treatment ◽  
Glutaric Aciduria Type ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Long Term Treatment

scholarly journals Recombinant Lactococcus lactis Carrying IL-4 and IL-10 Coding Vectors Protects against Type 1 Diabetes in NOD Mice and Attenuates Insulitis in the STZ-Induced Model

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Tatiane M. Preisser ◽  
Vanessa P. da Cunha ◽  
Mariana P. Santana ◽  
Vanessa B. Pereira ◽  
Denise C. Cara ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Islets ◽  
Lactococcus Lactis ◽  
Combined Treatment ◽  
Nod Mice ◽  
Eukaryotic Expression ◽  
Expression Vectors ◽  
Bacterial Strains ◽  
Long Term Treatment

Type 1 diabetes (T1D) is an autoimmune disease that culminates in beta cell destruction in the pancreas and, subsequently, deficiency in insulin production. Cytokines play a crucial role in the development of diabetes, orchestrating the recruitment and action of immune cells, to not only destroy insulin-producing cells but also preserve them. Therefore, the aim of this study was to investigate the effect of orally administered Lactococcus lactis MG1363 FnBPA+ strains carrying plasmids encoding IL-4 and IL-10 in the streptozotocin- (STZ-) induced diabetes model and in nonobese diabetic (NOD) mice. The STZ-induced mice that were treated with combined bacterial strains carrying plasmids encoding IL-4 and IL-10 showed lower incidence of diabetes and more preserved pancreatic islets than the mice that received the individual bacterial strains. Combined administration of L. lactis MG1363 FnBPA+ (pValac::dts::IL-4) and L. lactis MG1363 FnBPA+ (pValac::IL-10) resulted in protection against diabetes in NOD mice. It was shown that the combined treatment with recombinant bacterial by oral route prevented hyperglycemia and reduced the pancreatic islets-destruction in NOD mice. In addition, increased levels of IL-4 and IL-10 in serum and pancreatic tissue revealed a systemic effect of the treatment and also favored an anti-inflammatory microenvironment. Reduced concentrations of IL-12 in pancreas were essential to the regulation of inflammation, resulting in no incidence of diabetes in treated NOD mice. Normal levels of intestinal sIgA after long-term treatment with the L. lactis strains carrying plasmids encoding IL-4 and IL-10 indicate the development of oral tolerance and corroborate the use of this potent tool of mucosal delivery. For the first time, L. lactis MG1363 FnBPA+ strains carrying eukaryotic expression vectors encoding IL-4 and IL-10 are tested in STZ-induced and NOD mouse models. Therefore, our study demonstrates this innovative strategy provides immunomodulatory potential for further investigations in T1D and other autoimmune diseases.

scholarly journals Function of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes: Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Vitro

Diabetes ◽  
2015 ◽  
Vol 64 (7) ◽  
pp. 2506-2512 ◽  
Author(s):  
Lars Krogvold ◽  
Oskar Skog ◽  
Görel Sundström ◽  
Bjørn Edwin ◽  
Trond Buanes ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Isolated Pancreatic Islets

scholarly journals Evaluation of Long-Term Treatment Effect in a Type 1 Diabetes Intervention Trial: Differences After Stimulation With Glucagon or a Mixed Meal

Diabetes Care ◽  
2014 ◽  
Vol 37 (5) ◽  
pp. 1384-1391 ◽  
Author(s):  
Paolo Pozzilli ◽  
Itamar Raz ◽  
Dana Peled ◽  
Dana Elias ◽  
Ann Avron ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Term Treatment ◽  
Intervention Trial ◽  
Mixed Meal ◽  
Long Term Treatment ◽  
Diabetes Intervention

Anti-Hypertensive Effect of Metoprolol in Spontaneously Hypertensive Rats

1976 ◽  
Vol 51 (s3) ◽  
pp. 443s-445s
Author(s):  
B. Ljung ◽  
B. Åblad ◽  
L. Drews ◽  
E. Fellenius ◽  
A. Kjellstedt ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Plasma Concentrations ◽  
Term Treatment ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Long Term Treatment ◽  
Portal Veins

1. Oral and intravenous administration of metoprolol to adult spontaneously hypertensive rats (SHR) with established hypertension lowered arterial blood pressure within 4 days of treatment. 2. Steady-state plasma concentrations of metoprolol were similar to those of patients during antihypertensive treatment with this drug. 3. The neuroeffector function of portal veins of SHR treated orally for 14 days or intravenously for 4 days was not impaired when studied in vitro. This is in contrast to previous findings after long-term treatment. 4. It is concluded that the anti-hypertensive effect of metoprolol in SHR in many respects resembles that observed in patients. It is suggested that impairment of vasomotor nerve control may contribute to the anti-hypertensive effect of β-adrenoreceptor antagonists.

scholarly journals Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway

2021 ◽  
Vol 22 (12) ◽  
pp. 6570
Author(s):  
Yue Lv ◽  
Rui-Can Cao ◽  
Hong-Bin Liu ◽  
Xian-Wei Su ◽  
Gang Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Reserve ◽  
Primordial Follicle ◽  
Term Treatment ◽  
New Drugs ◽  
Gene Profiling ◽  
Primordial Follicles ◽  
Long Term Treatment ◽  
Follicle Activation

A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.

scholarly journals Effect of Coxsackievirus B4 Infection on the Thymus: Elucidating Its Role in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Vol 9 (6) ◽  
pp. 1177
Author(s):  
Abdulaziz Alhazmi ◽  
Magloire Pandoua Nekoua ◽  
Hélène Michaux ◽  
Famara Sane ◽  
Aymen Halouani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Viral Infections ◽  
Lymphoid Organ ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Coxsackievirus B4

The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance. Insulin-like growth factor 2 (IGF2) is the dominant self-peptide of the insulin family expressed in mTECs and plays a crucial role in the intra-thymic programing of central tolerance to insulin-secreting islet β-cells. Coxsackievirus B4 (CVB4) can infect and persist in the thymus of humans and mice, thus hampering the T-cell maturation and differentiation process. The modulation of IGF2 expression and protein synthesis during a CVB4 infection has been observed in vitro and in vivo in mouse models. The effect of CVB4 infections on human and mouse fetal thymus has been studied in vitro. Moreover, following the inoculation of CVB4 in pregnant mice, the thymic function in the fetus and offspring was disturbed. A defect in the intra-thymic expression of self-peptides by mTECs may be triggered by CVB4. The effects of viral infections, especially CVB4 infection, on thymic cells and functions and their possible role in the pathogenesis of type 1 diabetes (T1D) are presented.

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