Dataset Information

Stem Cell Research Tools in Human Metabolic Disorders: An Overview.

ABSTRACT: Metabolic disorders are very common in the population worldwide and are among the diseases with the highest health utilization and costs per person. Despite the ongoing efforts to develop new treatments, currently, for many of these disorders, there are no approved therapies, resulting in a huge economic hit and tension for society. In this review, we recapitulate the recent advancements in stem cell (gene) therapy as potential tools for the long-term treatment of both inherited (lysosomal storage diseases) and acquired (diabetes mellitus, obesity) metabolic disorders, focusing on the main promising results observed in human patients and discussing the critical hurdles preventing the definitive jump of this approach from the bench to the clinic.

SUBMITTER: Ricci S

PROVIDER: S-EPMC8534517 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Stem Cell Research Tools in Human Metabolic Disorders: An Overview.

Ricci Serena S Cacialli Pietro P

Cells 20211007 10

Metabolic disorders are very common in the population worldwide and are among the diseases with the highest health utilization and costs per person. Despite the ongoing efforts to develop new treatments, currently, for many of these disorders, there are no approved therapies, resulting in a huge economic hit and tension for society. In this review, we recapitulate the recent advancements in stem cell (gene) therapy as potential tools for the long-term treatment of both inherited (lysosomal stora ...[more]

PMID: 34685661

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Project description:Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the IKs potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings.

Project description:ObjectiveCurrent studies lack a comprehensive understanding of the environmental factors influencing type 2 diabetes, hindering an in-depth grasp of the overall etiology. To address this gap, we utilized network science tools to highlight research trends, knowledge structures, and intricate relationships among factors, offering a new perspective for a profound understanding of the etiology.MethodsThe Web of Science database was employed to retrieve documents relevant to environmental risk factors in type 2 diabetes from 2012 to 2024. Bibliometric analysis using Microsoft Excel and OriginPro provided a detailed scientific production profile, including articles, journals, countries, and authors. Co-occurrence analysis was employed to determine the collaboration state and knowledge structures, utilizing social network tools such as Gephi, Tableau, and R Studio. Additionally, theme evolutionary analysis was conducted using SciMAT to offer insights into research trends.ResultsThe publications and themes related to environmental factors in type 2 diabetes have consistently risen, shaping a well-established research domain. Lifestyle environmental factors, particularly diet and nutrition, stand out as the most represented and rapidly growing topics. Key focal hotspots include sedentary and digital behavior, PM2.5, ethnicity and socioeconomic status, traffic and greenspace, and depression. The theme evolutionary analysis revealed three distinct paths: (1) oxidative stress-air pollutants-PM2.5-air pollutants; (2) calcium-metabolic syndrome-cardiovascular disease; and (3) polychlorinated biphenyls (PCBs)-persistent organic pollutants (POPs)-obesity.ConclusionsDigital behavior signifies a novel approach for preventing and managing type 2 diabetes. The influence of PM2.5 and calcium on oxidative stress and abnormal vascular contraction is intricately linked to microvascular diabetes complications. The transition from PCBs and POPs to obesity underscores the disruption of endocrine function by chemicals, elevating the risk of diabetes. Future studies should explore the connections between environmental factors, microvascular complications, and long-term outcomes in diabetes.

Dataset Information

Stem Cell Research Tools in Human Metabolic Disorders: An Overview.

Publications

Stem Cell Research Tools in Human Metabolic Disorders: An Overview.

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