TY - JOUR T1 - Quantitative evaluation of human bone mesenchymal stem cells rescuing fulminant hepatic failure in pigs JF - Gut JO - Gut SP - 955 LP - 964 DO - 10.1136/gutjnl-2015-311146 VL - 66 IS - 5 AU - Dongyan Shi AU - Jianing Zhang AU - Qian Zhou AU - Jiaojiao Xin AU - Jing Jiang AU - Longyan Jiang AU - Tianzhou Wu AU - Jiang Li AU - Wenchao Ding AU - Jun Li AU - Suwan Sun AU - Jianzhou Li AU - Ning Zhou AU - Liyuan Zhang AU - Linfeng Jin AU - Shaorui Hao AU - Pengcheng Chen AU - Hongcui Cao AU - Mingding Li AU - Lanjuan Li AU - Xin Chen AU - Jun Li Y1 - 2017/05/01 UR - http://gut.bmj.com/content/66/5/955.abstract N2 - Objective Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells’ activities. Our objective was to clarify stem cell-recipient interactions for overcoming barriers to clinical application.Design We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells’ activities. The control and transplantation groups of pigs (n=15 per group) both received a D-galactosamine (D-Gal) injection (1.5 g/kg). The transplantation group received hBMSCs via intraportal vein infusion (3×106 cells/kg) immediately after D-Gal administration. The stem cell-recipient interactions were quantitatively evaluated by biochemical function, cytokine array, metabolite profiling, transcriptome sequencing and immunohistochemistry.Results All pigs in the control group died within an average of 3.22 days, whereas 13/15 pigs in the transplantation group lived >14 days. The cytokine array and metabolite profiling analyses revealed that hBMSC transplantation suppressed D-Gal-induced life-threatening cytokine storms and stabilised FHF within 7 days, while human-derived hepatocytes constituted only ∼4.5% of the pig hepatocytes. The functional synergy analysis of the observed profile changes indicated that the implanted hBMSCs altered the pigs’ cytokine responses to damage through paracrine effects. Delta-like ligand 4 was validated to assist liver restoration in both pig and rat FHF models.Conclusions Our results delineated an integrated model of the multifaceted interactions between stem cells and recipients, which may open a new avenue to the discovery of single molecule-based therapeutics that simulate stem cell actions. ER -