Siepe Matthias, Thomsen Andreas R, Duerkopp Natalie, Krause Ulf, Förster Katharina, Hezel Philip, Beyersdorf Friedhelm, Schlensak Christian, Südkamp Norbert P, Bosse Roland, Niemeyer Philipp
Department of Cardiovascular Surgery, University Medical Center Freiburg, Freiburg, Germany.
Tissue Eng Part A. 2009 Jul;15(7):1787-96. doi: 10.1089/ten.tea.2008.0356.
Mesenchymal stromal cells represent an attractive cell population for cell transplantation and tissue engineering purposes. The aim of this study was to search for neonatal thymus-derived mesenchymal stromal cells (nTMSC) and further characterize the differentiation and immunomodulatory properties thereof. The thymus glands of 13 infants undergoing congenital cardiac surgery were removed. After in vitro isolation and expansion, we identified adherent stromal cells with substantial proliferation potential. As characterized by FACS, the pattern of surface antigen expression of nTMSC resembled bone marrow stromal cells. Full mesenchymal differentiation potential is maintained during proliferation as confirmed by cultures for osteogenic, chondrogenic, and adipogenic lineages. After 5-azacytidine enrichment, morphological characteristics of cardiomyocytes were achieved. For immunologic investigations, the influence of nTMSC on the proliferative behavior of peripheral blood mononuclear cells was studied as a measure of the immune response. The nTMSC did not stimulate an allogeneic reaction in this coculture. Further, the expression of immunologically relevant markers was measured. Alike MSC from other origins, nTMSC did not express MHC-II. In contrast to mature MSC, some nTMSC even lack the expression of MHC-I. Our results confirm that the neonatal thymus contains mesenchymal stromal cells (nTMSC) with full mesenchymal differentiation potential and immunomodulatory properties.
间充质基质细胞是细胞移植和组织工程领域颇具吸引力的细胞群体。本研究旨在寻找源自新生儿胸腺的间充质基质细胞(nTMSC),并进一步表征其分化和免疫调节特性。收集了13例接受先天性心脏手术的婴儿的胸腺。经体外分离和扩增后,我们鉴定出具有显著增殖潜能的贴壁基质细胞。通过流式细胞术(FACS)表征,nTMSC的表面抗原表达模式类似于骨髓基质细胞。如通过成骨、软骨和脂肪生成谱系培养所证实,在增殖过程中nTMSC保持了完全的间充质分化潜能。经5-氮杂胞苷富集后,细胞呈现出心肌细胞的形态特征。对于免疫学研究,我们研究了nTMSC对外周血单个核细胞增殖行为的影响,以此作为免疫反应的一项指标。在这种共培养中,nTMSC未刺激同种异体反应。此外,我们检测了免疫相关标志物的表达。与其他来源的间充质干细胞(MSC)一样,nTMSC不表达MHC-II。与成熟的MSC不同,一些nTMSC甚至缺乏MHC-I的表达。我们的结果证实,新生儿胸腺含有具有完全间充质分化潜能和免疫调节特性的间充质基质细胞(nTMSC)。