Nour Ebrahim | Kazan Federal University (original) (raw)
Papers by Nour Ebrahim
Research Square (Research Square), Mar 22, 2024
Mesenchymal stromal cells (MSCs) show great potential in the eld of regenerative medicine due to ... more Mesenchymal stromal cells (MSCs) show great potential in the eld of regenerative medicine due to their multipotent differentiation capabilities and immunomodulatory properties. However, the characterization and classi cation of MSCs, particularly those derived from the pancreas, remains challenging, leading to a proliferation of terminology in the literature. Here, we present a comprehensive study elucidating the successful isolation of human pancreas-derived mesenchymal stromal cells (hPD-MSCs) from pancreatic tissue, their immortalization using lentiviral transduction of hTERT, and the maintenance of characteristic spindle-shaped morphology over extended passages. Flow cytometry analysis con rms the expression of classical MSC markers CD90, CD73, CD105, and CD44, along with CD106 (VCAM-1), indicative of immunomodulatory potential. Moreover, hPD-MSCs exhibit multilineage differentiation capacity into adipogenic and osteogenic lineages. Transcriptomic analysis reveals distinct gene expression pro les, highlighting similarities to pancreatic stellate cells (PSCs) and identifying speci c genes that characterize hPD-MSCs in comparison with mesenchymal cells of different origins. Notably, among these genes, hPD-MSCs exhibit differential expression in genes associated with pancreatic function, such as ISL1, and neural development (for example, NPTX1 and ZNF804A). The analysis also reveals a gene with an unknown function (ENSG00000286190). Our ndings contribute to the understanding of hPD-MSCs and their potential in regenerative medicine, particularly in pancreatic pathology.
Frontiers in Molecular Biosciences, Dec 15, 2022
Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diab... more Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diabetes are still largely directed at symptoms, aiming to control the manifestations of the pathology. This creates an overall need to find alternative measures that can impact on the causes of the disease, reverse diabetes, or make it more manageable. Understanding the role of key players in the pathogenesis of diabetes and the related β-cell functions is of great importance in combating diabetes. PDX1 is a master regulator in pancreas organogenesis, the maturation and identity preservation of β-cells, and of their role in normal insulin function. Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation), while in other types of diabetes, PDX1 expression is reduced. Therefore, alternative approaches to treat diabetes largely depend on knowledge of PDX1 regulation, its interaction with other transcription factors, and its role in obtaining β-cells through differentiation and transdifferentiation protocols. In this article, we review the basic functions of PDX1 and its regulation by genetic and epigenetic factors. Lastly, we summarize different variations of the differentiation protocols used to obtain β-cells from alternative cell sources, using PDX1 alone or in combination with various transcription factors and modified culture conditions. This review shows the unique position of PDX1 as a potential target in the genetic and cellular treatment of diabetes.
Molecular Diagnosis & Therapy
Research Square (Research Square), Mar 22, 2024
Mesenchymal stromal cells (MSCs) show great potential in the eld of regenerative medicine due to ... more Mesenchymal stromal cells (MSCs) show great potential in the eld of regenerative medicine due to their multipotent differentiation capabilities and immunomodulatory properties. However, the characterization and classi cation of MSCs, particularly those derived from the pancreas, remains challenging, leading to a proliferation of terminology in the literature. Here, we present a comprehensive study elucidating the successful isolation of human pancreas-derived mesenchymal stromal cells (hPD-MSCs) from pancreatic tissue, their immortalization using lentiviral transduction of hTERT, and the maintenance of characteristic spindle-shaped morphology over extended passages. Flow cytometry analysis con rms the expression of classical MSC markers CD90, CD73, CD105, and CD44, along with CD106 (VCAM-1), indicative of immunomodulatory potential. Moreover, hPD-MSCs exhibit multilineage differentiation capacity into adipogenic and osteogenic lineages. Transcriptomic analysis reveals distinct gene expression pro les, highlighting similarities to pancreatic stellate cells (PSCs) and identifying speci c genes that characterize hPD-MSCs in comparison with mesenchymal cells of different origins. Notably, among these genes, hPD-MSCs exhibit differential expression in genes associated with pancreatic function, such as ISL1, and neural development (for example, NPTX1 and ZNF804A). The analysis also reveals a gene with an unknown function (ENSG00000286190). Our ndings contribute to the understanding of hPD-MSCs and their potential in regenerative medicine, particularly in pancreatic pathology.
Frontiers in Molecular Biosciences, Dec 15, 2022
Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diab... more Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diabetes are still largely directed at symptoms, aiming to control the manifestations of the pathology. This creates an overall need to find alternative measures that can impact on the causes of the disease, reverse diabetes, or make it more manageable. Understanding the role of key players in the pathogenesis of diabetes and the related β-cell functions is of great importance in combating diabetes. PDX1 is a master regulator in pancreas organogenesis, the maturation and identity preservation of β-cells, and of their role in normal insulin function. Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation), while in other types of diabetes, PDX1 expression is reduced. Therefore, alternative approaches to treat diabetes largely depend on knowledge of PDX1 regulation, its interaction with other transcription factors, and its role in obtaining β-cells through differentiation and transdifferentiation protocols. In this article, we review the basic functions of PDX1 and its regulation by genetic and epigenetic factors. Lastly, we summarize different variations of the differentiation protocols used to obtain β-cells from alternative cell sources, using PDX1 alone or in combination with various transcription factors and modified culture conditions. This review shows the unique position of PDX1 as a potential target in the genetic and cellular treatment of diabetes.
Molecular Diagnosis & Therapy