The Effect of Liver Donors’ Age, Gender and Metabolic State on Pancreatic Lineage Activation

Matei, Iulia; Meivar‐Levy, Irit; Lixandru, Daniela; Dima, Simona; Florea, I; Ilie, Veronica; Albulescu, Radu; Popescu, Irinel; Ferber, Sarah

doi:10.2217/rme-2020-0092

Cited by 3 publications

(2 citation statements)

References 39 publications

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“…A better identification of such susceptible cells would be able to deliver a more targeted therapy without potentially damaging innate tissular functions [ 71 , 72 ]. Moreover, the trans-differentiation capacity to endocrine pancreas is not influenced by age, gender or metabolic state heterogeneity among different liver donors [ 73 ].…”

Section: The Role Of Mirna Detection During Pancreatic Islets Transpl...mentioning

confidence: 99%

miRNAs as Biomarkers in Diabetes: Moving towards Precision Medicine

Angelescu

Andronic

Dima

et al. 2022

IJMS

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Diabetes mellitus (DM) is a complex metabolic disease with many specifically related complications. Early diagnosis of this disease could prevent the progression to overt disease and its related complications. There are several limitations to using existing biomarkers, and between 24% and 62% of people with diabetes remain undiagnosed and untreated, suggesting a large gap in current diagnostic practices. Early detection of the percentage of insulin-producing cells preceding loss of function would allow for effective therapeutic interventions that could delay or slow down the onset of diabetes. MicroRNAs (miRNAs) could be used for early diagnosis, as well as for following the progression and the severity of the disease, due to the fact of their pancreatic specific expression and stability in various body fluids. Thus, many studies have focused on the identification and validation of such groups or “signatures of miRNAs” that may prove useful in diagnosing or treating patients. Here, we summarize the findings on miRNAs as biomarkers in diabetes and those associated with direct cellular reprogramming strategies, as well as the relevance of miRNAs that act as a bidirectional switch for cell therapy of damaged pancreatic tissue and the studies that have measured and tracked miRNAs as biomarkers in insulin resistance are addressed.

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Section: The Role Of Mirna Detection During Pancreatic Islets Transpl...mentioning

confidence: 99%

miRNAs as Biomarkers in Diabetes: Moving towards Precision Medicine

Angelescu

Andronic

Dima

et al. 2022

IJMS

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“…Using this approach, ectopically expressed pancreatic specific transcription factors were shown to trigger to a comprehensive and irreversible process of transdifferentiation (TD) of liver into pancreatic cells. Ectopic pancreatic Transcription Factors (pTFs) were hypothesized to induce heritable, epigenetic alterations in liver cells, that in turn, cause broad alterations in the landscape of gene expression, thus altering cellular identity [2][3][4][5]. However, ectopic pTF expression has proven obligatory but insufficient for activating the pancreatic lineage in liver cells, as most human liver cells resisted the pTF-induced TD process, while just a minority of cells trans-differentiated in response to ectopic pTFs expression delivered by recombinant adenoviruses [6,7].…”

Section: Introductionmentioning

confidence: 99%

The role of DNA demethylation in liver to pancreas transdifferentiation

et al. 2022

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Background Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. Results The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. Conclusions Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.

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Phenotypic Assessment of Liver-Derived Cell Cultures during in vitro Expansion

et al. 2021

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Background: Liver cells represent an attractive source of cells for autologous regenerative medicine. The present study assesses the liver cells’ stability during in vitro expansion, as a prerequisite for therapeutic use. Results: The human liver cell cultures in this study were propagated efficiently in vitro for at least 12 passages. No significant changes in morphology, intracellular ultrastructures and characteristic markers expression were found during in vitro expansion of cells from all analyzed donors. However, expanded cells derived from male donors of >60 years old, lost the Y chromosome. Conclusion: Liver-derived cell cultures adopt a proliferative, stable mesenchymal phenotype, through an epithelial to mesenchymal transition process. The molecular and phenotypic changes of the cells during propagation are uniform, despite the heterogeneity of the different donors. Loss of Y chromosome occurs after cells’ propagation in elder male donors.

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The Effect of Liver Donors’ Age, Gender and Metabolic State on Pancreatic Lineage Activation

Cited by 3 publications

References 39 publications

miRNAs as Biomarkers in Diabetes: Moving towards Precision Medicine

miRNAs as Biomarkers in Diabetes: Moving towards Precision Medicine

The role of DNA demethylation in liver to pancreas transdifferentiation

Phenotypic Assessment of Liver-Derived Cell Cultures during in vitro Expansion

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