Dollet Pierre-Edouard, Ravau Joachim, André Floriane, Najimi Mustapha, Sokal Etienne, Lombard Catherine
Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Avenue Mounier 52, 1200 Bruxelles, Belgium.
Stem Cells Int. 2016;2016:9302537. doi: 10.1155/2016/9302537. Epub 2016 Nov 13.
Mesenchymal stromal cells (MSCs) are known to have potential therapeutic benefits for a number of diseases. However, many studies report low engraftment levels, regardless of the target organ. One possible explanation could be that MSCs do not express the necessary receptors for engraftment. Indeed, MSCs appear to use a similar mechanism to leukocytes to engraft into injured organs, relying on various receptors for rolling, firm adhesion, and transmigration. In this study, we conducted an extensive surface molecule screening of adult-derived human liver stem/progenitor cells (ADHLSC) in an attempt to shed some light on this subject. We observed that ADHLSCs lack expression of most of the costimulatory molecules tested. Furthermore, study of the adhesion molecule profile of ADHLSCs revealed that they do not express selectin ligands or LFA-1 which are, respectively, involved in the rolling process and the firm adhesion. In addition, ADHLSCs slightly express VLA-4 and lose expression of CXCR4 altogether on their surface during culture expansion. However, ADHLSCs express all the integrin couples and matrix metalloproteinases needed to bind and integrate the extracellular matrix once the endothelial barrier is crossed. Collectively, these results suggest that binding to the endothelium may be the critical weak point in the engraftment process.
间充质基质细胞(MSCs)已知对多种疾病具有潜在的治疗益处。然而,许多研究报告称,无论靶器官如何,其植入水平都很低。一种可能的解释是,MSCs不表达植入所需的必要受体。事实上,MSCs似乎利用与白细胞类似的机制植入受损器官,依赖于各种受体进行滚动、牢固黏附和迁移。在本研究中,我们对成人来源的人肝干细胞/祖细胞(ADHLSC)进行了广泛的表面分子筛选,试图阐明这一问题。我们观察到,ADHLSCs缺乏所测试的大多数共刺激分子的表达。此外,对ADHLSCs黏附分子谱的研究表明,它们不表达分别参与滚动过程和牢固黏附的选择素配体或LFA-1。此外,ADHLSCs在培养扩增过程中表面VLA-4表达轻微,而CXCR4表达完全丧失。然而,一旦穿过内皮屏障,ADHLSCs表达所有结合和整合细胞外基质所需的整合素对和基质金属蛋白酶。总体而言,这些结果表明,与内皮细胞的结合可能是植入过程中的关键薄弱环节。