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.Multi-modal management of aggressive vertebral hemangioma: A single center experience
Mohamed FAROUK ; Mohamed Ali KASSEM ; Ashraf EZZELDEIN ; Mohamed Mohsen AMEEN ; Ali Hassan ELMOKADEM ; Mohamed M ELSHERBINI
Journal of Cerebrovascular and Endovascular Neurosurgery 2025;27(1):40-49
Objective:
This study aims at spotlighting different lines of management of aggressive vertebral hemangioma (VH) through a retrospective analysis of single center experience.
Methods:
Patients diagnosed with aggressive VHs in a tertiary referral center were reviewed from 2014 through 2024. Data of patients who met the inclusion criteria were analyzed. Patients of all ages, both sexes, and all varieties of clinical presentation were included, only patients who underwent at least one intervention were included.
Results:
The study included nine patients, comprising six females and three males, with a mean age of 29.3 years (ranging from 14 to 46). Six patients underwent Trans-arterial embolization (TAE), of whom five underwent further surgical procedures, while one patient found TAE to be sufficient as a stand-alone management technique. Eight patients underwent surgical management, five of whom were pre-operatively embolized.
Conclusions
Aggressive VHs are rare, and their management is challenging. Most cases require a multi-modal management, especially when presented with neurological deficit. Pre-operative embolization and/or vertebroplasty are safe and useful tools to decrease intra-operative bleeding of such a vascular pathology in cases undergoing open surgical procedures.
5.Multi-modal management of aggressive vertebral hemangioma: A single center experience
Mohamed FAROUK ; Mohamed Ali KASSEM ; Ashraf EZZELDEIN ; Mohamed Mohsen AMEEN ; Ali Hassan ELMOKADEM ; Mohamed M ELSHERBINI
Journal of Cerebrovascular and Endovascular Neurosurgery 2025;27(1):40-49
Objective:
This study aims at spotlighting different lines of management of aggressive vertebral hemangioma (VH) through a retrospective analysis of single center experience.
Methods:
Patients diagnosed with aggressive VHs in a tertiary referral center were reviewed from 2014 through 2024. Data of patients who met the inclusion criteria were analyzed. Patients of all ages, both sexes, and all varieties of clinical presentation were included, only patients who underwent at least one intervention were included.
Results:
The study included nine patients, comprising six females and three males, with a mean age of 29.3 years (ranging from 14 to 46). Six patients underwent Trans-arterial embolization (TAE), of whom five underwent further surgical procedures, while one patient found TAE to be sufficient as a stand-alone management technique. Eight patients underwent surgical management, five of whom were pre-operatively embolized.
Conclusions
Aggressive VHs are rare, and their management is challenging. Most cases require a multi-modal management, especially when presented with neurological deficit. Pre-operative embolization and/or vertebroplasty are safe and useful tools to decrease intra-operative bleeding of such a vascular pathology in cases undergoing open surgical procedures.
6.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.
7.Multi-modal management of aggressive vertebral hemangioma: A single center experience
Mohamed FAROUK ; Mohamed Ali KASSEM ; Ashraf EZZELDEIN ; Mohamed Mohsen AMEEN ; Ali Hassan ELMOKADEM ; Mohamed M ELSHERBINI
Journal of Cerebrovascular and Endovascular Neurosurgery 2025;27(1):40-49
Objective:
This study aims at spotlighting different lines of management of aggressive vertebral hemangioma (VH) through a retrospective analysis of single center experience.
Methods:
Patients diagnosed with aggressive VHs in a tertiary referral center were reviewed from 2014 through 2024. Data of patients who met the inclusion criteria were analyzed. Patients of all ages, both sexes, and all varieties of clinical presentation were included, only patients who underwent at least one intervention were included.
Results:
The study included nine patients, comprising six females and three males, with a mean age of 29.3 years (ranging from 14 to 46). Six patients underwent Trans-arterial embolization (TAE), of whom five underwent further surgical procedures, while one patient found TAE to be sufficient as a stand-alone management technique. Eight patients underwent surgical management, five of whom were pre-operatively embolized.
Conclusions
Aggressive VHs are rare, and their management is challenging. Most cases require a multi-modal management, especially when presented with neurological deficit. Pre-operative embolization and/or vertebroplasty are safe and useful tools to decrease intra-operative bleeding of such a vascular pathology in cases undergoing open surgical procedures.
8.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.
9.Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs.
Shimaa O ALI ; Nancy N SHAHIN ; Marwa M SAFAR ; Sherine M RIZK
Journal of Zhejiang University. Science. B 2025;26(8):789-804
OBJECTIVES:
The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics. We investigated the role of endothelial progenitor cells (EPCs) in a pentylenetetrazole (PTZ)-induced rat seizure model. A selected panel of long noncoding RNAs (lncRNAs), which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway, was also targeted.
METHODS:
The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers, neurotrophic factors, and relevant lncRNA genes. Rat behavior was assessed using Y-maze test and open field test (OFT).
RESULTS:
EPCs mitigated seizure-associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits, as evidenced by improved performance in the Y-maze test and OFT. EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2, Pnky, Dlx1, APF, HOTAIR, and FLJ11812. EPCs also boosted vascular endothelial growth factor (VEGF) expression. The ameliorative effect achieved by EPCs was comparable to that produced by valproate.
CONCLUSIONS
These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
Animals
;
Pentylenetetrazole
;
RNA, Long Noncoding
;
Seizures/therapy*
;
Rats
;
Male
;
Endothelial Progenitor Cells/transplantation*
;
Rats, Sprague-Dawley
;
Kindling, Neurologic
;
Vascular Endothelial Growth Factor A/metabolism*
;
Disease Models, Animal
10.Association between prosthesis use to the physical functioning and quality of life among adult unilateral lower limb amputees: An analytical cross-sectional study
Gian Searle S. Alkuino ; Marvin N. Catoy ; Shieka Delanne G. Alo ; Chloie Ysabel B. Allanigue ; Sheen Queenae C. Catamin ; Sam Francesca P. Cirilo ; Walled T. Ali ; Francine Gaile D. Co ; Josephine R. Bundoc ; Ramon Jason M. Javier
Health Sciences Journal 2024;13(1):1-9
Introduction:
A prosthesis is an artificial assistive device designed to replace a missing body part (e.g., limb), secondary to a disease, injury or congenital deformities. Prostheses are often used to restore
functional capacity while improving the quality of life (QoL).
Methods:
An analytical cross-sectional study was conducted among adults aged 19 to 64 years who were
permanent residents in Luzon who had undergone unilateral lower leg amputation. This epidemiologic
study employed the Modified Barthel Index for activities of daily living (ADLs), the Frenchay Activities
Index for instrumental activities of daily living (IADLs), and the WHOQOL-BREF for QoL. Descriptive
and analytical statistics of the responses of the Lower Limb Amputees (LLA) were done. Prevalence odds
ratio (POR) was calculated, and statistical significance was determined.
Results:
Among 165 LLA respondents, only 47.88% used prostheses. Unilateral LLA who exhibited
greater independence in ADLs (POR=19.22), more actively performed IADLs (POR=5.51), and had good
QoL (POR=3.83) were more likely to have been using prosthesis. All these findings were statistically
significant.
Conclusion
This study revealed a statistically significant association between prosthesis use to the
physical functioning and QoL among adult unilateral LLAs. It showed that prosthetic use was likely linked
with improved performance in ADLs and IADLs, and better QoL compared to those without.
Quality of Life


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