Key Takeaways & Executive Findings
- •• hPD-MSCs exhibit classical MSC features including surface markers (CD90, CD73, CD105, CD44, CD106) and differentiation into adipogenic and osteogenic lineages. • Transcriptomic analysis reveals that hPD-MSCs share significant gene expression similarities with pancreatic stellate cells (PSCs), suggesting a potential lineage relationship. • Specific genes (ISL1, NPTX1, ZNF804A) distinguish hPD-MSCs from MSCs of other origins, implicating roles in pancreatic function and neural development. • A novel gene (ENSG00000286190) with unknown function was identified, offering a new avenue for research in pancreatic MSC biology.
Abstract
Background Mesenchymal stromal cells (MSCs) are recognized for their potential in regenerative medicine, attributed to their multipotent differentiation capabilities and immunomodulatory properties. Despite this potential, the classification and detailed characterization of MSCs, especially those derived from specific tissues like the pancreas, remains challenging leading to a proliferation of terminology in the literature. This study aims to address these challenges by providing a thorough characterization of human pancreatic islets-derived mesenchymal stromal cells (hPD-MSCs). Methods hPD-MSCs were isolated from donor islets using enzymatic digestion, immortalized through lentiviral transduction of human telomerase reverse transcriptase (hTERT). Cells were characterized by immunostaining, flow cytometry and multilineage differentiation potential into adipogenic and osteogenic lineages. Further a transcriptomic analysis was done to compare the gene expression profiles of hPD-MSCs with other mesenchymal cells. Results We show that hPD-MSCs express the classical MSC features, including morphological characteristics, surface markers expression (CD90, CD73, CD105, CD44, and CD106) and the ability to differentiate into both adipogenic and osteogenic lineages. Furthermore, transcriptomic analysis revealed distinct gene expression profiles, showing notable similarities between hPD-MSCs and pancreatic stellate cells (PSCs). The study also identified specific genes that distinguish hPD-MSCs from MSCs of other origins, including genes associated with pancreatic function (e.g., ISL1) and neural development (e.g., NPTX1, ZNF804A). A novel gene with an unknown function (ENSG00000286190) was also discovered. Conclusions This study enhances the understanding of hPD-MSCs, demonstrating their unique characteristics and potential applications in therapeutic strategies. The identification of specific gene expression profiles differentiates hPD-MSCs from other mesenchymal cells and opens new avenues for research into their role in pancreatic function and neural development.
1. Introduction
Recent progress in stem cell biology and regenerative medicine has given rise to translational research aimed at repairing damaged tissues and restoring their proper cellular functions. MSCs stand out as an important candidate in the field of cellular therapy, having undergone extensive investigation and clinical trials. The therapeutic benefits of MSCs lie in their ease of extraction, ability to differentiate into various cell types, minimal immune response, and, most significantly, the substances they release, which have been demonstrated to mitigate damaged tissues [1].
Despite the prospective advantages of MSCs, practical constraints arise due to the inherent challenges associated with the isolation process and heterogeneity arising from diverse donor characteristics [2]. While all MSCs share basic characteristics, studies have shown variances in genotype and phenotype expression profiles among MSCs of different sources including expression of certain surface markers, differentiation capacities, and immunomodulatory properties [3, 4]. These differences extend to the physiological functions of MSCs and their therapeutic potential in the treatment of diverse diseases.
This highlights the significance of a nuanced characterization of MSCs for effective utilization in clinical applications, considering logistical, practical, and in vivo attributes. MSCs were initially isolated from mononuclear cells derived from bone marrow (BM-MSCs); nevertheless, recent evidence suggests that MSCs are present in almost all human tissues [5]. Notably, the pancreas harbors distinct subpopulations of MSCs, with evidence indicating that these cells can be derived from exocrine tissue (acinar and ductal epithelial cells) [6–8], or islets [9, 10]. The precise etiology of these cells remains ambiguous, potentially arising from epithelial-mesenchymal tra
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Nour Ebrahim, Nikolay Kondratyev, Alexander Artyuhov, Alexei Timofeev, Nadya Gurskaya, Alexey Andrianov, Roman Izrailov, Egor Volchkov, Tatyana Dyuzheva, Elena Kopantseva, Ekaterina Kiseleva, Vera Golimbet, Erdem Dashinimaev (2026). Human pancreatic islet-derived stromal cells reveal combined features of mesenchymal stromal cells and pancreatic stellate cells. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03963-2
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Frequently Asked Questions
What are human pancreatic islet-derived stromal cells (hPD-MSCs)?
hPD-MSCs are mesenchymal stromal cells isolated from human pancreatic islets. They exhibit classical MSC features such as surface marker expression and multilineage differentiation potential, but also show unique gene expression profiles similar to pancreatic stellate cells.
How were hPD-MSCs characterized in this study?
hPD-MSCs were characterized using immunostaining, flow cytometry, and differentiation assays into adipogenic and osteogenic lineages. Additionally, transcriptomic analysis compared their gene expression profiles with other mesenchymal cells.
What are the key findings of the transcriptomic analysis?
The transcriptomic analysis revealed that hPD-MSCs share notable similarities with pancreatic stellate cells (PSCs). Specific genes such as ISL1, NPTX1, and ZNF804A distinguish hPD-MSCs from MSCs of other origins, and a novel gene (ENSG00000286190) with unknown function was discovered.
Why is this research significant for regenerative medicine?
This research provides a thorough characterization of hPD-MSCs, highlighting their unique features and potential applications in therapeutic strategies. Understanding their gene expression profiles may open new avenues for treating pancreatic diseases and neural conditions.
What is the potential clinical relevance of hPD-MSCs?
hPD-MSCs may be used in cell-based therapies for pancreatic regeneration and possibly neural repair, given their expression of genes associated with pancreatic function and neural development. Their immunomodulatory properties and differentiation capacity make them attractive candidates for regenerative medicine.
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