Raicevic Gordana, Najar Mehdi, Najimi Mustapha, El Taghdouini Adil, van Grunsven Leo A, Sokal Etienne, Toungouz Michel
Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Cytotherapy. 2015 Feb;17(2):174-85. doi: 10.1016/j.jcyt.2014.10.001. Epub 2014 Nov 21.
Stem cell therapy for liver diseases has recently emerged as a promising alternative to liver transplantation. Eligible cells should have an appropriate immunophenotype. The aim of the present study was to define the immunological profile of two human liver-derived mesenchymal stromal cell populations, namely, stem cells (ADHLSC) and hepatic stellate cells (HSC).
The study was conducted under normal and inflammatory conditions with the use of human bone marrow mesenchymal stromal cells (BM-MSC) as reference.
Like BM-MSC and ADHLSC, HSC were negative for hematopoietic (CD45) and endothelial (CD34) markers but positive for stromal markers. All cell types were constitutively positive for HLA class I and negative for human leukocyte antigen (HLA) class II and co-stimulatory molecules (CD80, CD86, CD134 and CD252). Inflammation induced the expression of CD40 in all cell types, but the highest values were observed on HSCs; high CD252 expression was only observed on HSC as compared with ADHLSC and BM-MSC. The expression of various adhesion molecules (CD54, CD58, CD106 and CD166) was dissimilar in these three cell types and was differentially influenced by inflammation as well. ADHLSC and HSC constitutively expressed the immunosuppressive molecule HLA-G, whereas CD274 expression was induced by inflammation, as in the case of BM-MSC. Moreover, all cell types expressed the two major natural killer ligands CD112 and CD115.
Toll-like receptors (TLR) 1, 3, 4 and 6 messenger RNA was expressed by both cell types, whereas TLR 2, 5, 7, 9 and 10 were only expressed by ADHLSC. Inflammation increased the expression of TLR 2 and 3 by ADHLSC and HSC. Finally, both liver-derived cell types were immunosuppressive because they inhibited the proliferation of mitogen-activated T cells.
干细胞疗法治疗肝脏疾病最近已成为肝移植的一种有前景的替代方法。合格的细胞应具有适当的免疫表型。本研究的目的是确定两种人肝源性间充质基质细胞群体的免疫特征，即干细胞（成人肝源性间充质干细胞，ADHLSC）和肝星状细胞（HSC）。
本研究在正常和炎症条件下进行，以人骨髓间充质基质细胞（BM-MSC）作为对照。
与BM-MSC和ADHLSC一样，HSC对造血标志物（CD45）和内皮标志物（CD34）呈阴性，但对基质标志物呈阳性。所有细胞类型对I类人 HLA 均呈组成性阳性，对II类人白细胞抗原（HLA）和共刺激分子（CD80、CD86、CD134和CD252）呈阴性。炎症诱导所有细胞类型中CD40的表达，但在HSC上观察到的表达值最高；与ADHLSC和BM-MSC相比，仅在HSC上观察到高CD252表达。这三种细胞类型中各种黏附分子（CD54、CD58、CD106和CD166）的表达不同，并且也受到炎症的不同影响。ADHLSC和HSC组成性表达免疫抑制分子HLA-G，而CD274的表达如BM-MSC一样由炎症诱导。此外，所有细胞类型均表达两种主要的自然杀伤配体CD112和CD115。
两种细胞类型均表达Toll样受体（TLR）1、3、4和6的信使RNA，而TLR 2、5、7、9和10仅由ADHLSC表达。炎症增加了ADHLSC和HSC中TLR 2和3的表达。最后，两种肝源性细胞类型均具有免疫抑制作用，因为它们抑制了丝裂原激活的T细胞的增殖。
