来自包皮的间充质基质细胞：组织分离、细胞表征及免疫生物学特性

Mesenchymal stromal cells from the foreskin: Tissue isolation, cell characterization and immunobiological properties.

作者信息

Najar Mehdi, Raicevic Gordana, André Thibaud, Fayyad-Kazan Hussein, Pieters Karlien, Bron Dominique, Toungouz Michel, Lagneaux Laurence

机构信息

Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.

出版信息

Cytotherapy. 2016 Mar;18(3):320-35. doi: 10.1016/j.jcyt.2015.11.013.

DOI:10.1016/j.jcyt.2015.11.013

PMID:26857227

Abstract

BACKGROUND AIMS

Because of their self-renewal capacity, multilineage potential and immunomodulatory properties, MSCs are an attractive tool for cell-based immunotherapy strategies. Foreskin, considered as a biological waste material, has been shown to be a reservoir of therapeutic cells.

METHODS

MSCs were isolated from different foreskin samples, maintained under in vitro culture and defined according to the International Society for Cellular Therapy (ISCT) criteria. We subsequently determined their main cell characteristics as well as their immunobiological properties. The following parameters were determined: (i) morphology and phenotype, (ii) proliferative and clonogenic potentials, (iii) tri-lineage differentiation ability, (iv) immunological profile, (v) immunomodulatory properties and (vi) protein and messenger RNA expression/secretion profile of immunoregulatory cytokines/factors as well as the pattern of toll-like receptors (TLRs). By using a pro-inflammatory cytokine cocktail, we also evaluated the influence of an inflammatory environment on their biology.

RESULTS

With a typical fibroblast-like morphology and an ISCT-compliant phenotype, foreskin-MSCs (FSK-MSCs) were highly proliferative and had a great clonogenic potential. They displayed multilineage capacities and interesting immunomodulatory properties. Of importance, FSK-MSCs were not immunogenetic and were further able to inhibit T-cell proliferation. We showed that several immunoregulatory cytokines and factors might be potentially involved in FSK-MSC immunomodulation with particular attention to hepatocyte growth factor and interleukin-11. Moreover, FSK-MSCs expressed several TLRs and were sensitive to the inflammatory environment by properly adjusting their profile and fate.

CONCLUSIONS

Foreskin represents a new alternative source for MSCs that is compliant with ISCT criteria. Their unique immunobiological properties allow consideration of FSK-MSCs as a valuable tolerogenic product for cell-based immunotherapy.

摘要

背景与目的

由于间充质干细胞（MSCs）具有自我更新能力、多向分化潜能和免疫调节特性，它们是基于细胞的免疫治疗策略中一种有吸引力的工具。包皮被视为一种生物废料，已被证明是治疗性细胞的储存库。

方法

从不同的包皮样本中分离出MSCs，在体外培养条件下进行培养，并根据国际细胞治疗协会（ISCT）的标准进行鉴定。随后我们确定了它们的主要细胞特征及其免疫生物学特性。测定了以下参数：（i）形态和表型；（ii）增殖和克隆形成潜能；（iii）三向分化能力；（iv）免疫谱；（v）免疫调节特性；（vi）免疫调节细胞因子/因子的蛋白质和信使核糖核酸表达/分泌谱以及 Toll 样受体（TLRs）模式。通过使用促炎细胞因子混合物，我们还评估了炎症环境对其生物学特性的影响。

结果

包皮间充质干细胞（FSK-MSCs）具有典型的成纤维细胞样形态和符合ISCT标准的表型，增殖能力强且具有很大的克隆形成潜能。它们具有多向分化能力和有趣的免疫调节特性。重要的是，FSK-MSCs 不具有免疫原性，并且能够进一步抑制 T 细胞增殖。我们表明，几种免疫调节细胞因子和因子可能潜在地参与了 FSK-MSC 的免疫调节，尤其关注肝细胞生长因子和白细胞介素-11。此外，FSK-MSCs 表达多种 TLRs，并通过适当调整其谱和命运对炎症环境敏感。