Merimi Makram, Lagneaux Laurence, Lombard Catherine A, Agha Douâa Moussa, Bron Dominique, Lewalle Philippe, Meuleman Nathalie, Najimi Mustapha, Sokal Etienne M, Najar Mehdi
Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, 1000, Brussels, Belgium.
Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, 1070, Brussels, Belgium.
Inflamm Res. 2021 Feb;70(2):229-239. doi: 10.1007/s00011-020-01428-9. Epub 2021 Jan 6.
OBJECTIVE: One of the main challenges in liver cell therapy is the replacement of damaged cells and the induction of a tolerogenic microenvironment to promote graft acceptance by the recipient. Adult-derived human liver stem/progenitor cells (ADHLSCs) are currently evaluated at the clinical levels as a promising pro-regenerative and immune-modulatory tool. The expression profile of several immunological molecules may influence the local immune-inflammatory response and, therefore, modulate the tissue healing process. To increase the quality and safety of ADHLSCs before transplantation requires an appropriate analysis and characterization of their pattern expression of immune-inflammatory-associated molecules. METHODS: The expression of 27 molecules belonging to T-cell co-stimulatory pathway, CD47 partners, Ikaros family, CD300 family and TNF family were analyzed using flow cytometry. We compared their expression profiles to PBMCs, hepatocytes and ADHLSCs in both expansion and after hepatogenic differentiation culture conditions. RESULTS: This original immuno-comparative screening revealed that liver cell populations do not constitutively present significant immunological pattern compared to PBMCs. Moreover, our findings highlight that neither the expansion nor the hepatogenic differentiation induces the expression of immune-inflammatory molecules. The detailed expression characteristics (percentage of positive cells and median fluorescence intensity) of each molecule were analyzed and presented. CONCLUSION: By analyzing 27 relevant molecules, our immuno-comparative screening demonstrates that ADHLSCs keep a non-immunogenic profile independent of their expansion or hepatogenic differentiation state. Accordingly, the immunological profile of ADHLSCs seems to support their safe and efficient use in liver tissue therapeutic repair strategy.
目的:肝细胞治疗的主要挑战之一是替换受损细胞并诱导产生耐受性微环境,以促进受体对移植物的接受。成人来源的人肝干细胞/祖细胞(ADHLSCs)目前正在临床水平进行评估,作为一种有前景的促进再生和免疫调节工具。几种免疫分子的表达谱可能会影响局部免疫炎症反应,从而调节组织愈合过程。在移植前提高ADHLSCs的质量和安全性需要对其免疫炎症相关分子的模式表达进行适当的分析和表征。 方法:使用流式细胞术分析属于T细胞共刺激途径、CD47伴侣、Ikaros家族、CD300家族和TNF家族的27种分子的表达。我们将它们的表达谱与外周血单个核细胞(PBMCs)、肝细胞以及处于扩增状态和肝源性分化培养条件后的ADHLSCs进行了比较。 结果:这项原始的免疫比较筛选显示,与PBMCs相比,肝细胞群体在组成上没有显著的免疫模式。此外,我们的研究结果表明,扩增和肝源性分化均未诱导免疫炎症分子的表达。分析并呈现了每种分子的详细表达特征(阳性细胞百分比和中位荧光强度)。 结论:通过分析27种相关分子,我们的免疫比较筛选表明,ADHLSCs保持非免疫原性特征,与它们的扩增或肝源性分化状态无关。因此,ADHLSCs的免疫学特征似乎支持它们在肝组织治疗修复策略中的安全有效应用。
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