Characterizing the secretome of licensed hiPSC-derived MSCs

被引:5
|
作者
Ramos, Yolande F. M. [1 ]
Tertel, Tobias [2 ]
Shaw, Georgina [3 ]
Staubach, Simon [2 ]
de Almeida, Rodrigo Coutinho [1 ]
Suchiman, Eka [1 ]
Kuipers, Thomas B. [4 ]
Mei, Hailiang [4 ]
Barry, Frank [3 ]
Murphy, Mary [3 ]
Giebel, Bernd [2 ]
Meulenbelt, Ingrid [1 ]
机构
[1] Leiden Univ, Dept Biomed Data Sci, Sect Mol Epidemiol, Med Ctr, LUMC Posizone S-05-P,POB 9600, NL-2300 RC Leiden, Netherlands
[2] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Essen, Germany
[3] Natl Univ Ireland Galway, Galway, Ireland
[4] Sequencing Anal Support Core, LUMC, Leiden, Netherlands
基金
欧盟地平线“2020”;
关键词
Cell therapy; hiPSCs; Induced mesenchymal stromal cells; Immunomodulation; Extracellular vesicles; Exosomes; RNA sequencing; STEM-CELLS; THERAPY; EXOSOMES;
D O I
10.1186/s13287-022-03117-2
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNF alpha and IFN gamma demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFKB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.
引用
收藏
页数:9
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