1.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
2.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
3.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
4.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
5.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
6.Prevalence of SARS-CoV-2 infection among urban cleaning and solid waste management workers during transmission of the Omicron variant in Brazil
Paulo Ricardo MARTINS-FILHO ; Joyce Thayane da Conceição DOS SANTOS ; Márcia Santos REZENDE ; Fernanda Oliveira DE CARVALHO ; Érica Santos DOS REIS ; Waneska de Souza BARBOZA ; Taise Ferreira CAVALCANTE ; Cliomar Alves DOS SANTOS ; Lucindo José QUINTANS-JÚNIOR ; Renata GRESPAN ; Cristiane Bani CORRÊA ; Tatiana Rodrigues DE MOURA ; Dulce Marta SCHIMIEGUEL ; Jullyana de Souza Siqueira QUINTANS ; Adriano Antunes DE SOUZA ARAÚJO
Epidemiology and Health 2023;45(1):e2023025-
This study estimated the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in urban cleaning and solid waste management workers during the transmission of the Omicron variant in one of the poorest regions of Brazil (the state of Sergipe). Nasopharyngeal swabs were collected from 494 workers, and the presence of SARS-CoV-2 RNA was tested by quantitative reverse-transcriptase polymerase chain reaction. Data on socio-demographic characteristics, comorbidities, vaccination status, mask use, and use of public transport to commute to the workplace were collected. The prevalence with a 95% confidence interval (CI) was calculated from the proportion of SARS-CoV-2 positive cases among the total number of individuals tested. The prevalence ratio (PR) with a 95% CI was the measure of association used to evaluate the relationship between SARS-CoV-2 infection and the exposure variables. The prevalence of SARS-CoV-2 infection was 22.5% (95% CI, 19.0 to 26.4). Individuals under the age of 40 had a higher prevalence of infection (PR, 1.53; 95% CI, 1.03 to 2.30) as well as those who did not believe in the protective effect of vaccines (PR, 1.78; 95% CI, 1.05 to 2.89). Our results indicate the need for better guidance on preventive measures against coronavirus disease 2019 among urban cleaning and solid waste management workers.