10 results on '"Jeyagaran A"'
Search Results
2. Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA
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Abiramy Jeyagaran, Max Urbanczyk, Shannon L. Layland, Frank Weise, and Katja Schenke-Layland
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Medicine ,Science - Abstract
Abstract Transplantation of stem cell-derived β-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach is the long differentiation timeline that generates a heterogeneous population of pancreatic endocrine cells. To address this limitation, an inducible lentiviral overexpression system of mature β-cell markers was introduced into human induced-pluripotent stem cells (hiPSCs). Following the selection of the successfully transduced hiPSCs, the cells were treated with doxycycline in the pancreatic progenitor induction medium to support their transition toward the pancreatic lineage. Cells cultured with doxycycline presented the markers of interest, NGN3, PDX1, and MAFA, after five days of culture, and glucose-stimulated insulin secretion assays demonstrated that the cells were glucose-responsive in a monolayer culture. When cultured as a spheroid, the markers of interest and insulin secretion in a static glucose-stimulated insulin secretion assay were maintained; however, insulin secretion upon consecutive glucose challenges was limited. Comparison to human fetal and adult donor tissues identified that although the hiPSC-derived spheroids present similar markers to adult insulin-producing cells, they are functionally representative of fetal development. Together, these results suggest that with optimization of the temporal expression of these markers, forward programming of hiPSCs towards insulin-producing cells could be a possible alternative for islet transplantation.
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- 2024
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3. Decorin improves human pancreatic β-cell function and regulates ECM expression in vitro
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Urbanczyk, Max, primary, Jeyagaran, Abiramy, additional, Zbinden, Aline, additional, Lu, Chuan-en, additional, Marzi, Julia, additional, Kuhlburger, Laurence, additional, Nahnsen, Sven, additional, Layland, Shannon L., additional, Duffy, Garry, additional, and Schenke-Layland, Katja, additional
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- 2023
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4. Management of Pediatric Complex Regional Pain Syndrome : A Scoping Review
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Ologbenla, Adedeji, Finley, Allen, Baerg, Krista, Tupper, Susan, and Jeyagaran, Piranavi
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pediatric ,pain management ,Medicine and Health Sciences ,complex regional pain syndrome ,crps ,Social and Behavioral Sciences ,chronic pain ,pediatric pain - Abstract
Introduction Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by pain that is out of proportion to the inciting trauma or stimulus in the context of autonomic, trophic, and motor changes (1,2). Though pediatric Complex regional pain syndrome (pCRPS) is rare with a minimum Canadian incidence of 1.14/100 000 children (3), outcomes can significantly affect patient function and quality of life e.g. missed school days, withdrawal from activities, mental health challenges, etc (4). There is no gold standard radiologic, laboratory or diagnostic test for pCRPS. In the adult world, numerous diagnostic criteria have been validated and used, with the most recent being the Budapest criteria (2). No diagnostic criteria have been validated for pCRPS. Due to the variability in presentation as well as the lack of gold standard test and validated diagnostic criteria, there often tends to be a delay in diagnosis of pCRPS (1,4,5). Patients often get referred to multiple specialists before a diagnosis is made (3,4,6). This delay in diagnosis is thought to lead to worse outcomes (3,4,6). There are a wide range of pharmacological (NSAIDS, anticonvulsants, antidepressants etc.), non-pharmacological (physiotherapy, TENS, psychotherapy, acupuncture, etc.) and invasive interventional approaches (nerve blocks, sympathetic blocks, spinal cord stimulation, etc.) to pCRPS management (2,3,7,8). Though a multi-disciplinary approach is generally thought to be the most effective, there is still a lot of treatment variability across different centres (3). Considering the high degree of treatment variability, there is a need to evaluate and summarize the current evidence while identifying gaps so at the very least, consensus guidelines can be formed for the management of pCRPS. Hence, we will conduct a scoping review of existing literature to evaluate the management of pCRPS. As our topic is a broad one, a scoping review is more appropriate compared to a traditional systematic review. With a scoping review, we can rigorously assess the range, and nature of research activity in pCRPS, summarize and disseminate practice changing findings while identifying gaps in the literature (9,10). Objectives: The purpose of this review is to evaluate the literature and determine the most effective ways of managing pCRPS, summarise the various outcomes of pCRPS and to identify any gaps in the literature where future research should be conducted.
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- 2022
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5. Type 1 diabetes and engineering enhanced islet transplantation
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Jeyagaran, Abiramy, primary, Lu, Chuan-en, additional, Zbinden, Aline, additional, Birkenfeld, Andreas L., additional, Brucker, Sara Y., additional, and Layland, Shannon L., additional
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- 2022
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6. Fluorescence lifetime metabolic mapping of hypoxia‐induced damage in pancreatic pseudo‐islets
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Zbinden, A., Carvajal Berrio, D.A., Urbanczyk, M., Layland, Shannon, Bosch, M., Fliri, S., Lu, C.-E., Jeyagaran, A., Loskill, P., Duffy, G.P., Schenke-Layland, Katja, and Publica
- Abstract
Pancreatic islet isolation from donor pancreases is an essential step for the transplantation of insulin‐secreting v‐cells as a therapy to treat type 1 diabetes mellitus. This process however damages islet basement membranes, which can lead to islet dysfunction or death. Posttransplantation, islets are further stressed by a hypoxic environment and immune reactions that cause poor engraftment and graft failure. The current standards to assess islet quality before transplantation are destructive procedures, performed on a small islet population that does not reflect the heterogeneity of large isolated islet batches. In this study, we incorporated fluorescence lifetime imaging microscopy (FLIM) into a pancreas‐on‐chip system to establish a protocol to noninvasively assess the viability and functionality of pancreatic v‐cells in a three‐dimensional in vitro model (= pseudo‐islets). We demonstrate how (pre‐) hypoxic v‐cell‐composed pseudo‐islets can be discriminated from healthy functional pseudo‐islets according to their FLIM‐based metabolic profiles. The use of FLIM during the pretransplantation pancreatic islet selection process has the potential to improve the outcome of v‐cell islet transplantation.
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- 2020
7. Fluorescence lifetime metabolic mapping of hypoxia‐induced damage in pancreatic pseudo‐islets
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Zbinden, Aline, primary, Carvajal Berrio, Daniel A., additional, Urbanczyk, Max, additional, Layland, Shannon L., additional, Bosch, Mariella, additional, Fliri, Sandro, additional, Lu, Chuan‐en, additional, Jeyagaran, Abiramy, additional, Loskill, Peter, additional, Duffy, Garry P., additional, and Schenke‐Layland, Katja, additional
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- 2020
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8. Fluorescence lifetime metabolic mapping of hypoxia‐induced damage in pancreatic pseudo‐islets
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Chuan-En Lu, Garry P. Duffy, Mariella Bosch, Max Urbanczyk, Aline Zbinden, Abiramy Jeyagaran, Peter Loskill, Sandro Fliri, Katja Schenke-Layland, Daniel A. Carvajal Berrio, and Shannon L. Layland
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endocrine system ,Fluorescence-lifetime imaging microscopy ,Graft failure ,endocrine system diseases ,medicine.medical_treatment ,Population ,Islets of Langerhans Transplantation ,General Physics and Astronomy ,01 natural sciences ,Fluorescence ,General Biochemistry, Genetics and Molecular Biology ,010309 optics ,Islets of Langerhans ,0103 physical sciences ,medicine ,Humans ,General Materials Science ,Hypoxia ,education ,Type 1 diabetes ,education.field_of_study ,geography ,geography.geographical_feature_category ,business.industry ,Insulin ,010401 analytical chemistry ,General Engineering ,General Chemistry ,Hypoxia (medical) ,medicine.disease ,Islet ,0104 chemical sciences ,Transplantation ,Diabetes Mellitus, Type 1 ,Cancer research ,medicine.symptom ,business - Abstract
Pancreatic islet isolation from donor pancreases is an essential step for the transplantation of insulin-secreting β-cells as a therapy to treat type 1 diabetes mellitus. This process however damages islet basement membranes, which can lead to islet dysfunction or death. Posttransplantation, islets are further stressed by a hypoxic environment and immune reactions that cause poor engraftment and graft failure. The current standards to assess islet quality before transplantation are destructive procedures, performed on a small islet population that does not reflect the heterogeneity of large isolated islet batches. In this study, we incorporated fluorescence lifetime imaging microscopy (FLIM) into a pancreas-on-chip system to establish a protocol to noninvasively assess the viability and functionality of pancreatic β-cells in a three-dimensional in vitro model (= pseudo-islets). We demonstrate how (pre-) hypoxic β-cell-composed pseudo-islets can be discriminated from healthy functional pseudo-islets according to their FLIM-based metabolic profiles. The use of FLIM during the pretransplantation pancreatic islet selection process has the potential to improve the outcome of β-cell islet transplantation.
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9. ECM Proteins Nidogen-1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions.
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Jeyagaran A, Urbanczyk M, Carvajal-Berrio D, Baldissera T, Kaiser PD, Kuhlburger L, Czemmel S, Nahnsen S, Duffy GP, Brucker SY, Layland SL, and Schenke-Layland K
- Abstract
Transplantation of donor islets of Langerhans is a potential therapeutic approach for patients with diabetes mellitus; however, its success is limited by islet death and dysfunction during the initial hypoxic conditions at the transplantation site. This highlights the need to support the donor islets in the days post-transplantation until the site is vascularized. It was previously demonstrated that the extracellular matrix (ECM) proteins nidogen-1 (NID1) and decorin (DCN) improve the functionality and survival of the β-cell line, EndoC-βH3, and the viability of human islets post-isolation. To advance the use of these ECM proteins toward a clinical application and elucidate the mechanisms of action in primary islets, the study assesses the effects of ECM proteins NID1 and DCN on isolated human donor islets cultured in normoxic and hypoxic conditions. NID1- and DCN-treatment restore β-cell functionality of human donor islets in a hypoxic environment through upregulation of genes involved in glycolytic pathways and reducing DNA fragmentation in hypoxic conditions comparable to normoxic control islets. The results demonstrate that the utilization of NID1 or DCN with islets of Langerhans may have the potential to overcome the hypoxia-induced cell death observed post-transplantation and improve transplant outcomes., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
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- 2024
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10. Heterogeneity of Endothelial Cells Impacts the Functionality of Human Pancreatic In Vitro Models.
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Urbanczyk M, Abuhelou A, Köninger M, Jeyagaran A, Carvajal-Berrio D, Kim E, Marzi J, Loskill P, Layland SL, and Schenke-Layland K
- Abstract
Endothelial cells (ECs) play a crucial role in maintaining tissue homeostasis and functionality. Depending on their tissue of origin, ECs can be highly heterogeneous regarding their morphology, gene and protein expression, functionality, and signaling pathways. Understanding the interaction between organ-specific ECs and their surrounding tissue is therefore critical when investigating tissue homeostasis, disease development, and progression. In vitro models often lack organ-specific ECs, potentially limiting the translatability and validity of the obtained results. The goal of this study was to assess the differences between commonly used EC sources in tissue engineering applications, including human umbilical vein ECs (HUVECs), human dermal microvascular ECs (hdmvECs), and human foreskin microvascular ECs (hfmvECs), and organ-specific human pancreatic microvascular ECs (hpmvECs), and test their impact on functionality within an in vitro pancreas test system used for diabetes research. Utilizing high-resolution Raman microspectroscopy and Raman imaging in combination with established protein and gene expression analyses and exposure to defined physical signals within microfluidic cultures, we identified that ECs exhibit significant differences in their biochemical composition, relevant protein expression, angiogenic potential, and response to the application of mechanical shear stress. Proof-of-concept results showed that the coculture of isolated human islets of Langerhans with hpmvECs significantly increased the functionality when compared with control islets and islets cocultured with HUVECs. Our study demonstrates that the choice of EC type significantly impacts the experimental results, which needs to be considered when implementing ECs into in vitro models.
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- 2024
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