Significant reduction of apoptosis induced via hypoxia and oxidative stress in isolated human islet by resveratrol

Keshtkar, Somayeh; Kaviani, Maryam; Jabbarpour, Zahra; Abdullah, Ismail H. Al; Aghdaei, Mahdokht Hossein; Nikeghbalian, Saman; Shamsaeefar, Alireza; Geramizadeh, Bita; Azarpira, Negar; Ghahremani, Mohammad Hossein

doi:10.1016/j.numecd.2020.04.011

Cited by 15 publications

(17 citation statements)

References 41 publications

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“…Currently, isolated islets are incubated in culture media for 24-72 hours ahead of transplantation, during which the cell quality is evaluated, the recipient is prepared, immunosuppressive drugs are administered, and/or the isolated islets are transported to other centers. Previous studies have shown that isolated islets are faced by hypoxia and oxidative stress during the culture period (Keshtkar et al, 2020[ 18 ], 2019[ 19 ]; Zheng et al, 2012[ 45 ]) and the initial post-transplantation days, leading to islet death, particularly via the mitochondria apoptosis pathway (Miao et al, 2006[ 23 ]; Padmasekar et al, 2013[ 26 ]).…”

Section: Discussionmentioning

confidence: 99%

“…Although the transplantation of islets is backed by encouraging results, some limitations exist, such as the shortage of organ donors and the loss of islets both in the pre-transplant culture period and subsequent to transplantation (Froud et al, 2005[ 10 ]). The disconnection of islets from the microvascular network and native niche leads to cell death, which continues during the culture period (Keshtkar et al, 2020[ 18 ]). Ahead of transplantation, the islet culture must adequately preserve the islet quality while the graft recipient is prepared and the isolated islets are transported to remote clinical centers for transplantation (Shapiro et al, 2017[ 37 ]).…”

Section: Introductionmentioning

confidence: 99%

“…Ahead of transplantation, the islet culture must adequately preserve the islet quality while the graft recipient is prepared and the isolated islets are transported to remote clinical centers for transplantation (Shapiro et al, 2017[ 37 ]). However, the culture period can lead to significant islet death triggered by hypoxia and oxidative stress (Keshtkar et al, 2020[ 18 ], 2019[ 19 ]). These insults induce apoptosis and decrease β-cell function, thereby exerting a negative impact on the outcome, sometimes even impeding transplantation (Arzouni et al, 2017[ 2 ]).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function

Keshtkar

Kaviani

Sarvestani

et al. 2020

EXCLI Journal; 19:Doc1064; ISSN 1611-2156

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function

Keshtkar

Kaviani

Sarvestani

et al. 2020

EXCLI Journal; 19:Doc1064; ISSN 1611-2156

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“…The early initiator of islet destruction is hypoxia that induces apoptosis in the beta cells. Hypoxia also induces oxidative stress through reactive oxygen species (ROS) overproduction that leads to apoptosis during pre- and posttransplantation [ 3 – 7 ]. In clinical setting, islet culturing is performed in order to prepare the graft recipient, quality control of the cells, and transportation to other centers [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, studies have shown that isolated islets alone are unable to cope with hypoxia and oxidative stress during culture period. It can lead to the destruction and dysfunction of islets [ 3 , 7 , 10 ]. Therefore, it is necessary to improve the culture period by clinically feasible methods to inhibit apoptosis and increase the quality of islets for better transplantation outcomes.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Preconditioned Wharton’s Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System

Keshtkar

Kaviani

Jabbarpour

et al. 2020

Stem Cells International

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Protection of isolated pancreatic islets against hypoxic and oxidative damage-induced apoptosis is essential during a pretransplantation culture period. A beneficial approach to maintain viable and functional islets is the coculture period with mesenchymal stem cells (MSCs). Hypoxia preconditioning of MSCs (Hpc-MSCs) for a short time stimulates the expression and secretion of antiapoptotic, antioxidant, and prosurvival factors. The aim of the present study was to evaluate the survival and function of human islets cocultured with Hpc-MSCs. Wharton’s jelly-derived MSCs were subjected to hypoxia (5% O2: Hpc) or normoxia (20% O2: Nc) for 24 hours and then cocultured with isolated human islets in direct and indirect systems. Assays of viability and apoptosis, along with the production of reactive oxygen species (ROS), hypoxia-inducible factor 1-alpha (HIF-1α), apoptotic pathway markers, and vascular endothelial growth factor (VEGF) in the islets, were performed. Insulin and C-peptide secretions as islet function were also evaluated. Hpc-MSCs and Nc-MSCs significantly reduced the ROS production and HIF-1α protein aggregation, as well as downregulation of proapoptotic proteins and upregulation of antiapoptotic marker along with increment of VEGF secretion in the cocultured islet. However, the Hpc-MSCs groups were better than Nc-MSCs cocultured islets. Hpc-MSCs in both direct and indirect coculture systems improved the islet survival, while promotion of function was only significant in the direct cocultured cells. Hpc potentiated the cytoprotective and insulinotropic effects of MSCs on human islets through reducing stressful markers, inhibiting apoptosis pathway, enhancing prosurvival factors, and promoting insulin secretion, especially in direct coculture system, suggesting the effective strategy to ameliorate the islet quality for better transplantation outcomes.

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Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening Platform

Rademakers,

Sthijns,

Paulino da Silva Filho

et al. 2023

Advanced Biology

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Oxidative stress leads to a lower success rate of clinical islet transplantation. Here, FDA‐approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro “pseudoislet” spheroids, which are pre‐incubated with 1280 different compounds and subjected to oxidative stress. Cell viability and oxidative stress levels are determined using a high‐throughput fluorescence microscopy pipeline. Initial screening on cell viability results in 59 candidates. The top ten candidates are subsequently screened for their potential to decrease induced oxidative stress, and eight compounds efficient reduction of induced oxidative stress in both alpha and beta cells by 2550%. After further characterization, the compound sulfisoxazole is found to be the most capable of reducing oxidative stress, also at short pre‐incubation times, which is validated in primary human islets, where low oxidative stress levels and islet function are maintained. This study shows an effective screening strategy with 3D cell aggregates based on cell viability and oxidative stress, which leads to the discovery of several compounds with antioxidant capacity. The top candidate, sulfisoxazole is effective after a 30 min pre‐incubation, maintains baseline islet function, and may help alleviate oxidative stress in pancreatic islets.

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Significant reduction of apoptosis induced via hypoxia and oxidative stress in isolated human islet by resveratrol

Cited by 15 publications

References 41 publications

Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function

Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function

Hypoxia-Preconditioned Wharton’s Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System

Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening Platform

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