Human pancreatic islet-derived stromal cells reveal combined features of mesenchymal stromal cells and pancreatic stellate cells

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.

Авторы
Ebrahim Nour 1, 6 , Kondratyev Nikolay 2 , Artyuhov Alexander 1, 3 , Timofeev Alexei 1 , Gurskaya Nadya 1 , Andrianov Alexey 4 , Izrailov Roman 4 , Volchkov Egor 3, 7 , Dyuzheva Tatyana 8 , Kopantseva Elena 3 , Kiseleva Ekaterina 5 , Golimbet Vera 2 , Dashinimaev Erdem 1, 6, 3, 9
Номер выпуска
1
Язык
Английский
Статус
Опубликовано
Том
15
Год
2024
Организации
  • 1 Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University
  • 2 Mental Health Research Center
  • 3 Research Institute of Molecular and Cellular Medicine, RUDN University
  • 4 Loginov Moscow Clinical Scientifc Center
  • 5 Research Institute for Systems Biology and Medicine
  • 6 Moscow Institute of Physics and Technology (State University)
  • 7 Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev, NMRCPHOI) of Ministry of Healthcare of the Russian Federation
  • 8 Department of Hospital Surgery, Sklifosovsky Institute for Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University)
  • 9 Institute of Medicine, Banzarov Buryat State University
Ключевые слова
Pancreatic mesenchymal stromal cells; Pancreatic stellate cells; transcriptome analysis; pancreatic islets; pancreas
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