TSG-6 as a biomarker to predict efficacy of human mesenchymal stem/progenitor cells (hMSCs) in modulating sterile inflammation in vivo

Human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other tissues are currently being administered to large numbers of patients even though there are no biomarkers that accurately predict their efficacy in vivo. Using a mouse model of chemical injury of the cornea, we found that bon...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-11, Vol.111 (47), p.16766-16771
Main Authors: Lee, Ryang Hwa, Yu, Ji Min, Foskett, Andrea M., Peltier, Grant, Reneau, John C., Bazhanov, Nikolay, Oh, Joo Youn, Prockop, Darwin J.
Format: Article
Language:English
Subjects:
Animals
Biological markers
Biological Sciences
Biomarkers
Biomarkers - metabolism
Bone marrow
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cornea
Cultured cells
Female
Humans
Inflammation
Inflammation - metabolism
Inflammation - pathology
Male
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Messenger RNA
Mice
Mice, Inbred BALB C
Physical trauma
Real-Time Polymerase Chain Reaction
Reverse transcriptase polymerase chain reaction
Rodents
Stem cells
Stromal cells
Tissues
TNF inhibitors
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Summary:Human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other tissues are currently being administered to large numbers of patients even though there are no biomarkers that accurately predict their efficacy in vivo. Using a mouse model of chemical injury of the cornea, we found that bone-marrow–derived hMSCs isolated from different donors varied widely in their efficacy in modulating sterile inflammation. Importantly, RT-PCR assays of hMSCs for the inflammation-modulating protein TSG-6 expressed by the TNFα-stimulated gene 6 ( TSG-6 or TNFAIP6 ) predicted their efficacy in sterile inflammation models for corneal injury, sterile peritonitis, and bleomycin-induced lung injury. In contrast, the levels of TSG-6 mRNA were negatively correlated with their potential for osteogenic differentiation in vitro and poorly correlated with other criteria for evaluating hMSCs. Also, a survey of a small cohort suggested that hMSCs from female donors compared with male donors more effectively suppressed sterile inflammation, expressed higher levels of TSG-6 , and had slightly less osteogenic potential. Significance The clinical trials with human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other tissues are proceeding even though cultures of the cells are heterogeneous and there is large variability among preparations of hMSCs due to differences among donors, culture conditions, and inconsistent tissue sampling. However, there is currently no in vitro bioassay for the evaluation of hMSC efficacy in vivo. Therefore, the value of the data obtained from current clinical trials may well be compromised by variations in the quality of the hMSCs used. This study provides, to our knowledge, the first biomarker that can predict the efficacy of hMSCs in suppressing sterile inflammation in vivo.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1416121111