Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russia, 117997.
Moscow Institute of Physics and Technology (State University), Dolgoprudny, Russia, 141701.
Stem Cell Res Ther. 2024 Oct 8;15(1):351. doi: 10.1186/s13287-024-03963-2.
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.
背景：间充质基质细胞（MSCs）因其多能分化能力和免疫调节特性，在再生医学中具有潜力。尽管具有这种潜力，但 MSCs 的分类和详细特征，特别是那些源自特定组织（如胰腺）的 MSCs，仍然具有挑战性，导致文献中术语的大量增加。本研究旨在通过对人胰腺胰岛衍生的间充质基质细胞（hPD-MSCs）进行全面表征来解决这些挑战。
方法：使用酶消化从供体胰岛中分离 hPD-MSCs，通过慢病毒转导人端粒酶逆转录酶（hTERT）进行永生化。通过免疫染色、流式细胞术和多谱系分化潜力分化为脂肪和成骨谱系来对细胞进行表征。进一步进行转录组分析，以比较 hPD-MSCs 与其他间充质细胞的基因表达谱。
结果：我们表明 hPD-MSCs 表达经典 MSC 特征，包括形态特征、表面标志物表达（CD90、CD73、CD105、CD44 和 CD106）和向脂肪和成骨谱系分化的能力。此外，转录组分析显示出独特的基因表达谱，显示 hPD-MSCs 与胰腺星状细胞（PSCs）之间存在显著相似性。该研究还确定了将 hPD-MSCs 与其他来源的 MSC 区分开来的特定基因，包括与胰腺功能（例如 ISL1）和神经发育（例如 NPTX1、ZNF804A）相关的基因。还发现了一个具有未知功能的新基因（ENSG00000286190）。
结论：本研究增强了对 hPD-MSCs 的理解，展示了它们的独特特征和在治疗策略中的潜在应用。特定基因表达谱的鉴定将 hPD-MSCs 与其他间充质细胞区分开来，并为研究它们在胰腺功能和神经发育中的作用开辟了新的途径。
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