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.

中文翻译：

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成人来源的人肝干/祖细胞免疫炎症相关分子的免疫比较筛选

客观的

肝细胞治疗的主要挑战之一是更换受损细胞和诱导耐受性微环境以促进接受者接受移植物。成人衍生的人肝干/祖细胞 (ADHLSCs) 目前在临床水平上被评估为一种有前途的促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。为了在移植前提高 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 伙伴、Ikaros 家族、CD300 家族和 TNF 家族的 27 个分子的表达。我们在扩增和肝源分化培养条件下将它们的表达谱与 PBMC、肝细胞和 ADHLSC 进行了比较。

结果

这种原始的免疫比较筛选显示，与 PBMC 相比，肝细胞群在组成上不呈现显着的免疫学模式。此外，我们的研究结果强调，无论是扩增还是肝源性分化都不会诱导免疫炎症分子的表达。分析并呈现了每个分子的详细表达特征（阳性细胞的百分比和中值荧光强度）。

结论

通过分析 27 个相关分子，我们的免疫比较筛选表明 ADHLSCs 保持非免疫原性特征，独立于它们的扩增或肝源分化状态。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和有效使用。