Patrikoski Mimmi, Sivula Jyrki, Huhtala Heini, Helminen Mika, Salo Fanny, Mannerström Bettina, Miettinen Susanna
Adult Stem Cell Group, Institute of Biosciences and Medical Technology (BioMediTech), and School of Health Sciences, University of Tampere, Tampere, Finland; Science Center, Tampere University Hospital, Tampere, Finland
Adult Stem Cell Group, Institute of Biosciences and Medical Technology (BioMediTech), and School of Health Sciences, University of Tampere, Tampere, Finland; Science Center, Tampere University Hospital, Tampere, Finland.
Stem Cells Transl Med. 2014 Oct;3(10):1220-30. doi: 10.5966/sctm.2013-0201. Epub 2014 Aug 13.
The potential of human adipose stem cells (ASCs) for regenerative medicine has received recognition owing to their ease of isolation and their multilineage differentiation capacity. Additionally, low immunogenicity and immunosuppressive properties make them a relevant cell source when considering immunomodulation therapies and allogeneic stem cell treatments. In the current study, immunogenicity and immunosuppression of ASCs were determined through mixed lymphocyte reactions. The immunogenic response was analyzed after cell isolation and expansion in fetal bovine serum (FBS), human serum (HS)-supplemented medium, and xeno-free and serum-free (XF/SF) conditions. Additionally, the immunophenotype and the secretion of CXC chemokine ligand 8 (CXCL8), CXCL9, CXCL10, C-C chemokine ligand 2 (CCL2), CCL5, interleukin 2 (IL-2), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-α, interferon-γ, transforming growth factor-β1, indoleamine 2,3-deoxygenase, Galectin-1, and Galectin-3 were analyzed. The results showed that ASCs were weakly immunogenic when expanded in any of the three conditions. The significantly strongest suppression was observed with cells expanded in FBS conditions, whereas higher ASC numbers were required to display suppression in HS or XF/SF conditions. In addition, statistically significant differences in protein secretion were observed between direct versus indirect cocultures and between different culture conditions. The characteristic immunophenotype of ASCs was maintained in all conditions. However, in XF/SF conditions, a significantly lower expression of CD54 (intercellular adhesion molecule 1) and a higher expression of CD45 (lymphocyte common antigen) was observed at a low passage number. Although culture conditions have an effect on the immunogenicity, immunosuppression, and protein secretion profile of ASCs, our findings demonstrated that ASCs have low immunogenicity and promising immunosuppressive potential whether cultured in FBS, HS, or XF/SF conditions.
人类脂肪干细胞(ASC)在再生医学中的潜力因其易于分离和多谱系分化能力而得到认可。此外,低免疫原性和免疫抑制特性使其成为免疫调节疗法和同种异体干细胞治疗中一种相关的细胞来源。在本研究中,通过混合淋巴细胞反应确定了ASC的免疫原性和免疫抑制作用。在胎牛血清(FBS)、人血清(HS)补充培养基以及无异种和无血清(XF/SF)条件下进行细胞分离和扩增后,分析了免疫原性反应。此外,还分析了免疫表型以及CXC趋化因子配体8(CXCL8)、CXCL9、CXCL10、C-C趋化因子配体2(CCL2)、CCL5、白细胞介素2(IL-2)、IL-4、IL-6、IL-10、IL-17A、肿瘤坏死因子-α、干扰素-γ、转化生长因子-β1、吲哚胺2,3-双加氧酶、半乳糖凝集素-1和半乳糖凝集素-3的分泌情况。结果表明,在三种条件中的任何一种条件下扩增时,ASC的免疫原性都较弱。在FBS条件下扩增的细胞表现出最强的抑制作用,而在HS或XF/SF条件下则需要更高数量的ASC才能表现出抑制作用。此外,在直接与间接共培养之间以及不同培养条件之间观察到蛋白质分泌存在统计学上的显著差异。在所有条件下,ASC的特征性免疫表型均得以维持。然而,在XF/SF条件下,在低传代次数时观察到CD54(细胞间黏附分子1)的表达显著降低,而CD45(淋巴细胞共同抗原)的表达升高。尽管培养条件对ASC的免疫原性、免疫抑制作用和蛋白质分泌谱有影响,但我们的研究结果表明,无论在FBS、HS还是XF/SF条件下培养,ASC都具有低免疫原性和良好的免疫抑制潜力。