Human bone marrow, umbilical cord or liver mesenchymal stromal cells fail to improve liver function in a model of CCl4-induced liver damage in NOD/SCID/IL-2Ry(null) mice

摘要

Background aims. Transplantation is the gold standard procedure for treating acute and chronic end-stage liver diseases. Given the shortage of organs, the development of cellular sources other than human liver is urgent. The main objective of this project was to examine the effect of mesenchymal stromal cell (MSC) (bone marrow, umbilical cord and liver MSCs) intravenous injection on liver regeneration in a model of hepatic damage in NOD/SCID/IL non-obese diabetic/severecombined immunodeficient/Interleukin-2Rg(null) (NSG) mice. Methods. Mice received 3 intraperitoneal injections of CCl4 Carbon tetrachloride per week for 4 weeks. Forty-eight hours after the last injection of CCl4, mice received 500,000 MSCs or phosphate-buffered saline by intravenous injection. We examined hepatic damage by means of quantitative image analysisand blood enzyme analysis 24 h, 1 week or 8 weeks after MSC or phosphate-buffered saline injection. We also examined MSC homing by means of real-time polymerase chain reaction of human albumin. Results. We adapted a model of liver injury in immunodeficient mice. In this model, accumulation of collagen in newly formed scar septa was apparent up to 8 weeks after CCl4 treatment. Human albumin DNA was found in all organs tested. However, intravenous MSC injection,even after CXCR4 C-X-C chemokine receptor type 4 transduction and whatever the origin of MSCs, failed to improve liver damage. Conclusions. In this liver injury model, MSCs were propagated in various tissues, particularly filtering organs. For the treatment of hepatic damage, intravenous administration of moderate doses of MSCs does not appear to be effective. Yet, this adapted liver injury model is appropriate for investigating engraftment of human cells.