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
Department of Functional Sciences, University of Medicine and Pharmacy "Victor Babes" Timisoara, Timisoara, Romania.
Electron Microscopy Integrated Laboratory, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath St., 400293, Cluj-Napoca, Romania.
Histochem Cell Biol. 2016 Aug;146(2):153-65. doi: 10.1007/s00418-016-1430-y. Epub 2016 Apr 16.
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.
胸腺细胞的发育以及成熟T细胞的生成是一个复杂的过程，需要胸腺细胞与胸腺微环境中的其他细胞进行时空相互作用。最近，间充质基质细胞从新生儿人类胸腺中分离出来，并分化为软骨生成、骨生成和脂肪生成谱系，就像它们在骨髓中的对应细胞一样。然而，它们在胸腺细胞稳态中的功能尚不清楚。在我们对大鼠间充质基质细胞和胸腺细胞进行的自体共培养中，基质细胞维持了培养的胸腺细胞的活力，并刺激了CD4-CD8-双阴性胸腺细胞的发育以及主要是CD4+单阳性胸腺细胞的成熟。胸腺细胞也会影响骨髓间充质基质细胞的干性，因为在共培养中，与细胞增殖和迁移相关的标志物CD44在它们中的表达会降低。间充质基质细胞对胸腺细胞发育的影响需要两种细胞之间的直接物理接触，且不是由可溶性因子介导的。当两种细胞在物理上分离时，间充质基质细胞对胸腺细胞的刺激作用就不会发生。电子显微镜证实了胸腺细胞和间充质基质细胞膜之间的紧密接触。我们的实验表明，间充质基质细胞和胸腺细胞之间可能会发生膜交换，比如CD44从间充质基质细胞转移到胸腺细胞，但它对胸腺细胞发育的功能意义仍有待确定。这些结果表明，间充质基质细胞通常可能是体内胸腺微环境的一部分，并形成一个能够维持和引导胸腺细胞发育的生态位。
