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 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.
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and rlee@medicine.tamhsc.edu Prockop@medicine.tamhsc.edu.
Ryang Hwa
RH
Lee
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and.
Ji Min
JM
Yu
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and.
Andrea M
AM
Foskett
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and.
Grant
G
Peltier
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and.
John C
JC
Reneau
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and.
Nikolay
N
Bazhanov
Department of Ophthalmology, Seoul National University Hospital, Jongno-gu, Seoul 110-744, Korea.
Joo Youn
JY
Oh
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502; and rlee@medicine.tamhsc.edu Prockop@medicine.tamhsc.edu.
Darwin J
DJ
Prockop
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction
D015415:Biomarkers; D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human
MPO; gender; myeloperoxidase; neutrophils