title: Mesenchymal stromal cells support the viability and differentiation of thymocytes through direct contact in autologous co-cultures.
abstract: The development of thymocytes and generation of mature T cells is a complex process that requires spatio-temporal interactions of thymocytes with the other cells of the thymus microenvironment. Recently, mesenchymal stromal cells were isolated from the neonatal human thymus and differentiated into chondrogenic, osteogenic, and adipogenic lineages, just like their bone marrow counterparts. However, their function in thymocyte homeostasis is unknown. In our autologous co-cultures of rat mesenchymal stromal cells and thymocytes, the stromal cells preserve the viability of cultured thymocytes and stimulate the development of CD4-CD8- double-negative and the maturation of mainly CD4+ single-positive thymocytes. Thymocytes also influence the stemness of bone marrow mesenchymal stromal cells, as their expression of CD44, a marker associated with cellular proliferation and migration, is reduced in co-cultures. Mesenchymal stromal cells' influence on thymocyte development requires direct physical contact between the two cells and is not mediated by a soluble factor. When the two types of cells were physically separated, the stimulative effects of mesenchymal stromal cells on thymocytes did not occur. Electron microscopy confirmed the close contact between the membranes of thymocytes and mesenchymal stromal cells. Our experiments suggest that membrane exchanges could occur between mesenchymal stromal cells and thymocytes, such as the transfer of CD44 from mesenchymal stromal cells to the thymocytes, but its functional significance for thymocytes development remains to be established. These results suggest that mesenchymal stromal cells could normally be a part of the in vivo thymic microenvironment and form a niche that could sustain and guide the development of thymocytes.
authors.affiliation: Department of Functional Sciences, University of Medicine and Pharmacy "Victor Babes" Timisoara, Timisoara, Romania.
authors.forename: Seyed Mohammad Reza
authors.initials: SM
authors.lastname: Azghadi
authors.affiliation: Electron Microscopy Integrated Laboratory, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath St., 400293, Cluj-Napoca, Romania.|Molecular Biology and Biotechnology Department, Faculty of Biology and Geology, Babeş-Bolyai University, 5-7 Clinicilor St., 400006, Cluj-Napoca, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Suciu
authors.affiliation: Regional Center of Immunology of Transplantation, Emergency Clinical County Hospital Timisoara, Timisoara, Romania. gruia_alexandra@yahoo.com.
authors.forename: Alexandra Teodora
authors.initials: AT
authors.lastname: Gruia
authors.affiliation: Center of Electron Microscopy, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Barbu-Tudoran
authors.affiliation: Regional Center of Immunology of Transplantation, Emergency Clinical County Hospital Timisoara, Timisoara, Romania.
authors.forename: Mirabela Iustina
authors.initials: MI
authors.lastname: Cristea
authors.affiliation: Department of Functional Sciences, University of Medicine and Pharmacy "Victor Babes" Timisoara, Timisoara, Romania.|INCD "Victor Babes", Bucharest, Romania.
authors.forename: Ani Aurora
authors.initials: AA
authors.lastname: Mic
authors.affiliation: Department of Pathophysiology, Center for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Danina
authors.initials: D
authors.lastname: Muntean
authors.affiliation: Regional Center of Immunology of Transplantation, Emergency Clinical County Hospital Timisoara, Timisoara, Romania.|Faculty of Animal Sciences and Biotechnologies, Banat's University of Agricultural Sciences and Veterinary Medicine, Timisoara, Romania.
authors.forename: Dragos Vasile
authors.initials: DV
authors.lastname: Nica
authors.affiliation: Department of Functional Sciences, University of Medicine and Pharmacy "Victor Babes" Timisoara, Timisoara, Romania.
authors.forename: Felix Aurel
authors.initials: FA
authors.lastname: Mic
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002470:Cell Survival; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors
keywords: Co-cultures; Maturation; Mesenchymal stromal cells; Thymocytes; Viability