Mesenchymal stem cells expanded in human platelet lysate display a decreased inhibitory capacity on T- and NK-cell proliferation and function

被引:113
作者
Abdelrazik, Heba [1 ,2 ,3 ,4 ]
Spaggiari, Grazia M. [1 ]
Chiossone, Laura [1 ]
Moretta, Lorenzo [1 ]
机构
[1] Ist Giannina Gaslini, I-16147 Genoa, Italy
[2] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy
[3] Univ Genoa, Ctr Eccellenza Ric Biomed, Genoa, Italy
[4] Cairo Univ, Fac Med, Cairo, Egypt
关键词
Graft-versus-host disease; Hematopoietic stem cell transplantation; Human platelet lysate; Mesenchymal stromal cells; NK cells; VERSUS-HOST-DISEASE; CLINICAL-GRADE PRODUCTION; FETAL BOVINE SERUM; STROMAL CELLS; CULTURE-CONDITIONS; ANIMAL SERUM; BONE-MARROW; SCALE EXPANSION; IDENTIFICATION; CYTOTOXICITY;
D O I
10.1002/eji.201141542
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
The use of fetal bovine serum (FBS) for the culture and expansion of mesenchymal stromal cells (MSCs) limits their possible clinical applications. Although some recent studies recommended substituting FBS with human platelet lysate (HPL) for the expansion of MSCs for clinical use, the functional capacity of the expanded cells has only been partially explored. 10% FBS and two other commercial FBS-containing media (MesenCult and MesenPro) were compared with 10% HPL-containing medium for their ability to support MSCs expansion and immunomodulation. We demonstrate that HPL sustained MSC proliferation and expansion in vitro. However, the cumulative cell numbers recovered were comparable with those obtained in MesenPro medium. Moreover, we show that HPL alters the expression of some relevant MSC surface molecules, namely the DNAM-1 ligands PVR and Nectin-2, the NKG2D ligand ULBP3, the adhesion molecules CD49d and alpha v beta 3 and the fibroblast-associated protein. In addition, MSCs cultured in HPL displayed impaired inhibitory capacity on T-cell proliferation to alloantigen and NK-cell proliferation and cytotoxicity. Finally, they showed decreased constitutive PGE2 production while IL-6, IL-8 and RANTES secretion were upregulated. These results imply some limitations in the use of HPL for the expansion of MSCs to be used as immunomodulators in clinical applications.
引用
收藏
页码:3281 / 3290
页数:10
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