Directly injected native bone-marrow stem cells cannot incorporate into acetaminophen-induced liver injury

Abstract

The paucity of liver donation highlights the use of cell-based strategies for end-stage liver failure. We recently showed that bone marrow-derived aggregates (BMDAs) can completely restore the hematopoietic system in gamma-irradiated mice. These aggregates are stem and progenitor cells in the bone marrow (BM), composed of both hematopoietic and non-hematopoietic lineages. Furthermore, reports showed that resident BM cells migrate to the liver and integrate themselves into the tissue in small numbers. Hence, we hypothesized that direct delivery of BMDAs to the damaged liver might enhance the integration of BM cells in the liver because of its stemness property, intact BM architecture, the physical proximity of these niche-like structures to the damaged sites and the existence of liver paracrine factors. To this aim, we made an acute liver model by intraperitoneal injection of acetaminophen. Then, GFP-expressing BMDAs were intrahepatically injected. Despite the detection of GFP-expressing cells five days after intrahepatic injection, these cells were not detectable at days 15 and 60, indicating that the puzzle of BM cell integration in the liver still has more missing pieces other than stemness, physical proximity, and paracrine factors. Actually, it seems that even intact BM structures need further signals to be qualified for integration.