Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features

• Published in: Current stem cell research and therapy 2020-04, Vol.11 (1), p.158-13, Article 158
• Main Authors: Villard, Orianne, Armanet, Mathieu, Couderc, Guilhem, Bony, Claire, Moreaux, Jerome, Noël, Daniele, De Vos, John, Klein, Bernard, Veyrune, Jean-Luc, Wojtusciszyn, Anne
• Format: Article
• Language: English
• Subjects: Adherent cells; Analysis; Binding sites; Bone marrow; Bone Marrow Cells; CD105 antigen; CD73 antigen; CD90 antigen; Cell culture; Cell Differentiation; Cell Proliferation; Cell therapy; Cells, Cultured; Chondrogenesis; Collagen; Conditioned medium; Diabetes; DNA microarrays; Extracellular matrix; Fibronectin; Fibronectins; Flow cytometry; Gene expression; Growth factors; Human health and pathology; Humans; Hybridization; Hépatology and Gastroenterology; Immunofluorescence; Immunoglobulins; Immunomodulation; Islet cells; Islets of Langerhans; Leukocytes, Mononuclear; Life Sciences; Mesenchymal Stem Cells; Mesenchymal stromal cells; Mesenchyme; Neomycin; Pancreas; Pancreas transplantation; Pancreatic islet transplantation; Pancreatic islets; Penicillin; Peripheral blood mononuclear cells; Proteins; Stem cells; Western blotting
• ISSN: 1757-6512; 1757-6512; 1574-888X
• DOI: 10.1186/s13287-020-01649-z

Mesenchymal stromal cells (MSCs) represent an interesting tool to improve pancreatic islet transplantation. They have immunomodulatory properties and secrete supportive proteins. However, the functional properties of MSCs vary according to many factors such as donor characteristics, tissue origin, or isolation methods. To counteract this heterogeneity, we aimed to immortalize and characterize adherent cells derived from human pancreatic islets (hISCs), using phenotypic, transcriptomic, and functional analysis. Adherent cells derived from human islets in culture were infected with a hTERT retrovirus vector and then characterized by microarray hybridization, flow cytometry analysis, and immunofluorescence assays. Osteogenic, adipogenic, and chondrogenic differentiation as well as PBMC proliferation suppression assays were used to compare the functional abilities of hISCs and MSCs. Extracellular matrix (ECM) gene expression profile analysis was performed using the SAM (Significance Analysis of Microarrays) software, and protein expression was confirmed by western blotting. hISCs kept an unlimited proliferative potential. They exhibited several properties of MSCs such as CD73, CD90, and CD105 expression and differentiation capacity. From a functional point of view, hISCs inhibited the proliferation of activated peripheral blood mononuclear cells. The transcriptomic profile of hISCs highly clusterized with bone marrow (BM)-MSCs and revealed a differential enrichment of genes involved in the organization of the ECM. Indeed, the expression and secretion profiles of ECM proteins including collagens I, IV, and VI, fibronectin, and laminins, known to be expressed in abundance around and within the islets, were different between hISCs and BM-MSCs. We generated a new human cell line from pancreatic islets, with MSCs properties and retaining some pancreatic specificities related to the production of ECM proteins. hISCs appear as a very promising tool in islet transplantation by their availability (as a source of inexhaustible source of cells) and ability to secrete a supportive "pancreatic" microenvironment.