Ramsperger-Gleixner Martina, Li Chang, Wallon Nina, Kuckhahn Annika, Weisbach Volker, Weyand Michael, Heim Christian
Department of Cardiac Surgery, University Hospital of Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany.
Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
J Clin Med. 2025 May 15;14(10):3474. doi: 10.3390/jcm14103474.
Mesenchymal stem cell-based therapy may be indicated in ischaemic heart disease. The use of autologous adipose-derived mesenchymal stromal cells (AdMSCs) offers regenerative potential due to their paracrine effects. The aim of this study was to expand and characterise adult human thymus-derived MSCs harvested during open heart surgery with respect to their stem cell and paracrine properties. : Enzymatically and non-enzymatically isolated human thymic AdMSCs (ThyAdMSCs) were cultured in xeno-free media containing pooled human platelet lysate (pPL). MSC characterisation was performed. Ex vivo expanded ThyAdMSCs were differentiated into three lineages. Proliferative capacity and immunomodulatory properties were assessed by proliferation assays and mixed lymphocyte reaction, respectively. Gene expression analysis was performed by qPCR. Both isolation methods yielded fibroblast-like cells with plastic adherence and high proliferation. Flow cytometry revealed distinct expression of MSC markers in the absence of haematopoietic cell surface markers. Ex vivo expanded ThyAdMSCs could be differentiated into adipocytes, osteocytes, and chondrocytes. Activated peripheral blood mononuclear cells were significantly reduced when co-cultured with ThyAdMSCs, indicating their ability to inhibit immune cells in vitro. Gene expression analysis showed significantly less IFNγ and TNFα, indicating an alteration of the activated and pro-inflammatory state in the presence of ThyAdMSCs. : These results demonstrate an efficient method to generate AdMSCs from human thymus. These MSCs have a strong immunomodulatory capacity and are, therefore, a promising cell source for regenerative medicine. The culture conditions are crucial for cells to proliferate in culture. Further research could explore the use of ThyAdMSCs or their secretome in surgical procedures.
基于间充质干细胞的疗法可能适用于缺血性心脏病。使用自体脂肪来源的间充质基质细胞（AdMSCs）因其旁分泌作用而具有再生潜力。本研究的目的是扩增并鉴定在心脏直视手术期间采集的成人人类胸腺来源的间充质干细胞（MSCs）的干细胞特性和旁分泌特性。：将通过酶法和非酶法分离的人类胸腺AdMSCs（ThyAdMSCs）在含有混合人血小板裂解物（pPL）的无血清培养基中培养。对MSCs进行了鉴定。将体外扩增的ThyAdMSCs分化为三个谱系。分别通过增殖试验和混合淋巴细胞反应评估增殖能力和免疫调节特性。通过qPCR进行基因表达分析。两种分离方法均产生了具有贴壁生长和高增殖能力的成纤维细胞样细胞。流式细胞术显示在缺乏造血细胞表面标志物的情况下MSCs标志物有明显表达。体外扩增的ThyAdMSCs可分化为脂肪细胞、骨细胞和软骨细胞。与ThyAdMSCs共培养时，活化的外周血单个核细胞显著减少，表明其在体外抑制免疫细胞的能力。基因表达分析显示IFNγ和TNFα显著减少，表明在存在ThyAdMSCs的情况下活化和促炎状态发生了改变。：这些结果证明了一种从人胸腺生成AdMSCs的有效方法。这些MSCs具有强大的免疫调节能力，因此是再生医学中一种有前景的细胞来源。培养条件对于细胞在培养中的增殖至关重要。进一步的研究可以探索在外科手术中使用ThyAdMSCs或其分泌组。
