Fayyad-Kazan Mohammad, Najar Mehdi, Fayyad-Kazan Hussein, Raicevic Gordana, Lagneaux Laurence
Institute of Molecular Biology and Medicine, Université Libre de Bruxelles (ULB), Gosselies, Belgium.
Laboratory of Clinical Cell Therapy, Université Libre de Bruxelles (ULB), Institut Jules Bordet, Brussels, Belgium.
Med Sci Monit Basic Res. 2017 Mar 24;23:87-96. doi: 10.12659/msmbr.903518.
BACKGROUND Mesenchymal stromal cells (MSCs) possess potent immunomodulatory properties that increase their value as a cell-based therapeutic tool for managing various immune-based disorders. Over the past years, accumulated results from trials using MSCs-based therapy have shown substantial contradictions. Although the reasons underlying these discrepancies are still not completely understood, it is well known that the immunomodulatory activities mediated by distinct MSCs differ in a manner dependent on their tissue origin and adequate response to inflammation priming. Thus, characterization of new molecular pathway(s) through which distinct MSC populations can exert their immunomodulatory effects, particularly during inflammation, will undoubtedly enhance their therapeutic potential. MATERIAL AND METHODS After confirming their compliance with ISCT criteria, quantitative real time-PCR (qRT-PCR) was used to screen new immunoregulatory genes in MSCs, derived from adipose tissue, foreskin, Wharton's jelly or the bone-marrow, after being cultivated under normal and inflammatory conditions. RESULTS FGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals. CONCLUSIONS Our observations suggest that these identified immunoregulatory genes may be considered as potential candidates to be targeted in order to enhance the immunomodulatory properties of MSCs towards more efficient clinical use.
背景 间充质基质细胞(MSCs)具有强大的免疫调节特性,这增加了其作为基于细胞的治疗工具来管理各种免疫相关疾病的价值。在过去几年中,使用基于MSCs治疗的试验积累的结果显示出巨大的矛盾。尽管这些差异背后的原因仍未完全理解,但众所周知,不同MSCs介导的免疫调节活性因其组织来源和对炎症引发的适当反应而有所不同。因此,确定不同MSC群体发挥免疫调节作用的新分子途径,特别是在炎症期间,无疑将增强其治疗潜力。
材料与方法 在确认符合国际细胞治疗协会(ISCT)标准后,采用定量实时PCR(qRT-PCR)筛选来自脂肪组织、包皮、脐带华通氏胶或骨髓的MSCs在正常和炎症条件下培养后的新免疫调节基因。
结果 FGL2、GAL、SEMA4D、SEMA7A和IDO1基因在不同的MSC群体中似乎存在差异转录。此外,在MSCs暴露于炎症信号后,这些基因的调节方式也不相同。
结论 我们的观察结果表明,这些已确定的免疫调节基因可被视为潜在的靶点,以增强MSCs的免疫调节特性,使其在临床应用中更有效。