Mesenchymal stromal cells support the viability and differentiation of thymocytes through direct contact in autologous co-cultures

• Published in: Histochemistry and cell biology 2016-08, Vol.146 (2), p.153-165
• Main Authors: Azghadi, Seyed Mohammad Reza, Suciu, Maria, Gruia, Alexandra Teodora, Barbu-Tudoran, Lucian, Cristea, Mirabela Iustina, Mic, Ani Aurora, Muntean, Danina, Nica, Dragos Vasile, Mic, Felix Aurel
• Format: Article
• Language: English
• Subjects: Animals; Autografts; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bone marrow; CD4 antigen; CD44 antigen; CD8 antigen; Cell Adhesion; Cell Biology; Cell Differentiation; Cell proliferation; Cell Survival; Cellular biology; Coculture Techniques; Developmental Biology; Electron microscopy; Female; Flow Cytometry; Functional anatomy; Gene expression; Homeostasis; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Immune system; Leukocytes; Lymphocytes T; Male; Maturation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Microscopy, Confocal; Microscopy, Electron; Neonates; Original Paper; Rats; Rats, Sprague-Dawley; Stromal cells; Thymocytes; Thymocytes - cytology; Thymocytes - metabolism; Thymus
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-016-1430-y

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.