scholarly journals Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue.

2020 ◽  
Author(s):  
Claudia Jara ◽  
Felipe Oyarzun-Ampuero ◽  
Flavio Carrión ◽  
Esteban González-Echeverría ◽  
Claudio Cappelli ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Sodium Alginate ◽  
Islet Cells ◽  
Type I Diabetes ◽  
Human Mesenchymal Stem Cells ◽  
Autoimmune Response ◽  
Type I ◽  
Strict Diet ◽  
Cellular Aggregates

Abstract Background: In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients is still a challenge. For these reasons, it is necessary to explore new cellular sources and immunological isolation methods oriented to develop T1DM cell-based therapies. Aims: We postulate human adipose-derived stem cell (hASC) as an adequate source to generate pancreatic islet cells in vitro, and to produce islet-like structures. Furthermore, we propose microencapsulation of these aggregates as an immunological isolation strategy. Methods: hASC obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells. Then, insulin producing cells (IPC) and glucagon producing cells (GPC) were later cocultured in low adhesion conditions to form cellular aggregates, and later encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed. Results: The results show that multipotent hASC efficiently differentiate to IPC and GPC, and express pancreatic markers, including insulin or glucagon hormones which they secrete upon stimulation (5 fold for insulin in IPC, and 4 fold for glucagon, compared to undifferentiated cells. In turn, calculation of the Feret diameter and area of cellular aggregates revealed, finding mean diameters ~80 µm and 65 % of the aggregates reached 4000 µm2 at 72h of formation. IPC/GPC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable when stabilized with Ba2+, yielding average diameters ~300 µm. Interestingly, Ba2+-microencapsulated aggregates respond to high external glucose with insulin secretion. Conclusions: The IPC/GPC differentiation process from hASC, followed by the generation of cellular aggregates that are later microencapsulated, could represent a possible treatment for T1DM.

scholarly journals Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue.

2020 ◽  
Author(s):  
Claudia Jara ◽  
Felipe Oyarzun-Ampuero ◽  
Flavio Carrión ◽  
Esteban González-Echeverría ◽  
Claudio Cappelli ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Sodium Alginate ◽  
Islet Cells ◽  
Type I Diabetes ◽  
Human Mesenchymal Stem Cells ◽  
Autoimmune Response ◽  
Type I ◽  
Strict Diet ◽  
Cellular Aggregates

Abstract Background: In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients is still a challenge. For these reasons, it is necessary to explore new cellular sources and immunological isolation methods oriented to develop T1DM cell-based therapies. Aims: We postulate human adipose-derived stem cell (hASC) as an adequate source to generate pancreatic islet cells in vitro, and to produce islet-like structures. Furthermore, we propose microencapsulation of these aggregates as an immunological isolation strategy. Methods: hASC obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells. Then, insulin producing cells (IPC) and glucagon producing cells (GPC) were later cocultured in low adhesion conditions to form cellular aggregates, and later encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed. Results: The results show that multipotent hASC efficiently differentiate to IPC and GPC, and express pancreatic markers, including insulin or glucagon hormones which they secrete upon stimulation (5 fold for insulin in IPC, and 4 fold for glucagon, compared to undifferentiated cells. In turn, calculation of the Feret diameter and area of cellular aggregates revealed, finding mean diameters ~80 µm and 65 % of the aggregates reached 4000 µm2 at 72h of formation. IPC/G PC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable when stabilized with Ba2+, yielding average diameters ~300 µm. Interestingly, Ba2+-microencapsulated aggregates respond to high external glucose with insulin secretion. Conclusions: The IPC/GPC differentiation process from hASC, followed by the generation of cellular aggregates that are later microencapsulated, could represent a possible treatment for T1DM.

scholarly journals Microencapsulation of cellular aggregate composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue.

2020 ◽  
Author(s):  
Claudia Jara ◽  
Felipe Oyarzun-Ampuero ◽  
Flavio Carrión ◽  
Esteban González-Echeverría ◽  
Claudio Cappelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Glycemic Control ◽  
Sodium Alginate ◽  
Type I Diabetes ◽  
Human Mesenchymal Stem Cells ◽  
Autoimmune Response ◽  
Type I ◽  
Cellular Aggregates

Abstract Background. In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients still a challenge. Methods Human adipose-derived mesenchymal stem cells (hASC) obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells (IPC and GPC respectively). Then, we cocultured IPC and GPC cells in low adhesion conditions to form cellular aggregates, which were encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed. Results We demonstrated that multipotent hASC efficiently differentiate to IPC and GPC, which also express pancreatic markers, including insulin or glucagon hormones. In turn, we calculated the Feret diameter of cellular aggregates, finding mean diameters ~80 µm at 72h of incubation. IPC/GPC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable in Ba 2+ stabilized microgels, with average diameters ~300 µm. Interestingly, Ba 2+ -microencapsulated aggregates respond to high external glucose with insulin secretion. Conclusions The IPC/GPC differentiation process from hASC followed by generate cellular aggregates in vitro, that once microencapsulated could represent a possible treatment to T1DM.

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus

Diabetes ◽  
1984 ◽  
Vol 33 (4) ◽  
pp. 394-400 ◽  
Author(s):  
G. Bolli ◽  
P. De Feo ◽  
S. De Cosmo ◽  
G. Perriello ◽  
G. Angeletti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Type I Diabetes ◽  
Type I Diabetes Mellitus ◽  
Type I ◽  
Short Term

scholarly journals Patterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 249
Author(s):  
Ruediger Goess ◽  
Ayse Ceren Mutgan ◽  
Umut Çalışan ◽  
Yusuf Ceyhun Erdoğan ◽  
Lei Ren ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Islet Cells ◽  
Human Pancreatic Cancer ◽  
Type I ◽  
Type Iv ◽  
Pancreatic Cancer Cells

Background: Pancreatic cancer‐associated diabetes mellitus (PC‐DM) is present in most patients with pancreatic cancer, but its pathogenesis remains poorly understood. Therefore, we aimed to characterize tumor infiltration in Langerhans islets in pancreatic cancer and determine its clinical relevance. Methods: Langerhans islet invasion was systematically analyzed in 68 patientswith pancreatic ductal adenocarcinoma (PDAC) using histopathological examination and 3D in vitro migration assays were performed to assess chemoattraction of pancreatic cancer cells to isletcells. Results: Langerhans islet invasion was present in all patients. We found four different patterns of islet invasion: (Type I) peri‐insular invasion with tumor cells directly touching the boundary, but not penetrating the islet; (Type II) endo‐insular invasion with tumor cells inside the round islet; (Type III) distorted islet structure with complete loss of the round islet morphology; and (Type IV)adjacent cancer and islet cells with solitary islet cells encountered adjacent to cancer cells. Pancreatic cancer cells did not exhibit any chemoattraction to islet cells in 3D assays in vitro. Further, there was no clinical correlation of islet invasion using the novel Islet Invasion Severity Score (IISS), which includes all invasion patterns with the occurrence of diabetes mellitus. However, Type IV islet invasion was related to worsened overall survival in our cohort. Conclusions: We systematically analyzed, for the first time, islet invasion in human pancreatic cancer. Four different main patterns of islet invasion were identified. Diabetes mellitus was not related to islet invasion. However, moreresearch on this prevailing feature of pancreatic cancer is needed to better understand underlying principles.

scholarly journals Periodontal disease and type I diabetes mellitus: Associations with glycemic control and complications

2013 ◽  
Vol 17 (5) ◽  
pp. 597 ◽  
Author(s):  
Ajita Meenawat ◽  
Karan Punn ◽  
Vivek Srivastava ◽  
AnandS Meenawat ◽  
RS Dolas ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Periodontal Disease ◽  
Type I Diabetes ◽  
Type I Diabetes Mellitus ◽  
Type I

DISTINCTIVE FEATURES OF PROCOAGULANT RESPONSE OF MONOCYTES FROM DIABETIC PATIENTS

1987 ◽  
Author(s):  
B JUDE ◽  
A WATEL ◽  
D FONTAINE ◽  
P FONTAINE ◽  
A COSSON
Keyword(s):  
Type I Diabetes ◽  
Vascular Complications ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Diabetic Patients ◽  
Type I ◽  
Factor X ◽  
Female Ratio ◽  
Male Female Ratio

Hypercoagulability is one of the possible factors reported in genesis or aggravation of vascular complications in diabetes mellitus. We therefore examined procoagulant activity (PCA) of disrupted monocytes frcm 26 patients with Type I diabetes and 6 with Type II, versus 32 control subjects (male/ female ratio = 1 in each group).Diabetes monocytes exhibited a slight but detectable PCA before any incubation or in vitro stimulation, whereas control monocytes did not. Data obtained with coagulation factor deficient plasmas or phospholipase C indicated that PCA was tissue factor (TF) alone in 22 cases and TF associated with a significant amount of factor VII/VIIa activity in 10 cases.Incubation in serum free medium led to significant raise of PCA in diabetes cells when stimulated with endotoxin or not, and in control cells only after stimulation. Furthermore, PCA appeared earlier in diabetes monocytes than in control ones, (4 hours, versus 20 hours). PCA frcm control cells was FT-like. PCA frcm diabetes cells was FT-like when no VII/VIIa activity was present on non-stimulated cells, and prothrombinase-like when VII/VIIa activity was early associated with the cells. In the latter case, trace amounts of factor X activity were also detectable. Whether factor VII and factor X activities were of plasmatic origin and associated to the cells, or synthesized in vitro by the cells remains unclear. The characteristics of PCA were net correlated with clinical features (age, diabetic complications) nor with the type of diabetes.Our data suggest that in diabetes patients, monocytes exhibit an increased PCA, possibly corresponding to a baseline stimulation, or at least a higher responsiveness to undergoing stimuli in vitro.

scholarly journals Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse.

1987 ◽  
Vol 165 (6) ◽  
pp. 1639-1654 ◽  
Author(s):  
L S Wicker ◽  
B J Miller ◽  
L Z Coker ◽  
S E McNally ◽  
S Scott ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Dominant Gene ◽  
Nod Mouse ◽  
Autoimmune Response ◽  
Type I ◽  
Diabetes In Animals ◽  
Nonobese Diabetic ◽  
Control Of Diabetes ◽  
Insulin Dependent ◽  
Or Gene

Genetic analysis of the development of diabetes and insulitis has been performed in the nonobese diabetic (NOD) mouse strain, a model of insulin-dependent (type I) diabetes mellitus. (NOD X C57BL/10)F1, F2, and (F1 X NOD) first-, second-, and third-backcross generations were studied. The data obtained were consistent with the hypothesis that diabetes is controlled by at least three functionally recessive diabetogenic genes, or gene complexes, one of which is linked to the MHC of the NOD. In contrast, pancreatic inflammation leading to insulitis was found to be controlled by a single incompletely dominant gene. One of the two diabetogenic loci that is not linked to the MHC appears to be essential for the development of severe insulitis. This diabetogenic gene may be identical to the gene that controls the initiation of the autoimmune response that progresses to insulitis. Although this gene appears to be functionally recessive in its control of diabetes, it is incompletely dominant in its control of insulitis. The MHC-linked diabetogenic gene, although not required for the development of insulitis, apparently influences the progression of the autoimmune response since NOD MHC homozygotes in the backcross generations displayed the highest incidence and most severe cases of insulitis. Interestingly, we have found two MHC heterozygous backcross females that have become diabetic, suggesting that either the MHC-linked diabetogenic gene is not strictly recessive or that a recombination event has occurred between the diabetogenic gene and the K or I-A regions of the MHC. The third diabetogenic locus appears to influence the progression of severe insulitis to overt diabetes. In animals homozygous at this locus, diabetes may result from a decreased ability to develop a protective suppressor response to the autoimmune process.

scholarly journals The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell cytotoxicity

2004 ◽  
Vol 382 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Michael WELSH ◽  
Charlotte WELSH ◽  
Maria EKMAN ◽  
Johan DIXELIUS ◽  
Robert HÄGERKVIST ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Type I Diabetes ◽  
Type I ◽  
Β Cell ◽  
Main Site

Hallmarks of the inflammatory process in Type I diabetes are macrophage activation, local release of β-cell-toxic cytokines and infiltration of cytotoxic T lymphocytes. We have observed recently that mice overexpressing active FRK (fyn-related kinase)/RAK (previously named GTK/Bsk/IYK, where GTK stands for gut tyrosine kinase, Bsk for β-cell Src-homology kinase and IYK for intestinal tyrosine kinase) in β-cells exhibit increased susceptibility to β-cell-toxic events, and therefore, we now attempt to find a more precise role for FRK/RAK in these processes. Phosphopeptide mapping of baculovirus-produced mouse FRK/RAK revealed an autophosphorylation pattern compatible with Tyr-394 being the main site. No evidence for in vitro phosphorylation of the C-terminal regulatory sites Tyr-497 and Tyr-504 was obtained, nor was there any indication of in vitro regulation of FRK/RAK kinase activity. Screening a panel of known tyrosine kinase inhibitors for their ability to inhibit FRK/RAK revealed several compounds that inhibited FRK/RAK, with a potency similar to that reported for their ability to inhibit other tyrosine kinases. Cytokine-induced islet toxicity was reduced in islets isolated from FRK/RAK knockout mice and this occurred without effects on the production of nitric oxide. Addition of the nitric oxide inhibitor nitroarginine to FRK/RAK knockout islets exposed to cytokines decreased cell death to a basal level. In normal islets, cytokine-induced cell death was inhibited by the addition of two FRK/RAK inhibitors, SU4984 and D-65495, or by transfection with short interfering RNA against FRK/RAK. It is concluded that FRK/RAK contributes to cytokine-induced β-cell death, and inhibition of this kinase could provide means to suppress β-cell destruction in Type I diabetes.

Sign in / Sign up

Export Citation Format

Share Document