Simultaneous Administration of NOD-2 (MDP) and TLP-4 (LPS) Ligands to Bone Marrow Donors 24 h before Transplantation Increases the Content of Multipotent Stromal Cells (MSCs) in Bone Marrow Grafts in CBA Mice Compared to the Total Result of Their Isolated Administration

Abstract

In 3-month bone marrow transplants of CBA mice from bone marrow donors receiving single injections of TLR-4 ligand (LPS) or NOD-2 ligand (muramyl dipeptide, MDP) 24 h before transplantation, an increase in the total number of MSCs (by 2.6 and 1.9 times, respectively), as well as a slight increase in the number of nuclear cells and the mass of bone capsules (by 1.3 and 1.2 times) were observed. After combined administration of MDР and LPS to donors, the total content of MSCs in the grafts was higher by 1.6 times in comparison with the total result of their isolated administration (and by 7.2 times in comparison with the control). At the same time, the concentration of osteogenic MSCs in the grafts of all groups was almost the same and corresponded to the control level. The number of nuclear cells and the mass of bone capsules of the grafts after combined administration of LPS and MDP were close (~80%) to the sum of the results of their isolated administration. These findings suggest that activation of the stromal tissue and the success of bone marrow transplantation depend on the intensity of innate immune responses. These data can be useful for the development of optimal methods of tissue transplantation.

Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin

“…Interesting data on a 1.9-fold increase in the number of multipotent bone marrow stem cells were obtained in bone marrow transplants of mice from bone marrow donors who received single injections of MDP 24 h before transplantation [121]. These results confirm previously obtained data on the correction of cytopenia during chemotherapy [119].…”

Calycosin inhibits hepatocyte apoptosis in acute liver failure by suppressing the TLR4/NF‐κB pathway: An in vitro study

“…Therefore, LPS is commonly used in scientific research to induce liver injury in the ALF models. Animal model studies have shown that LPS‐induced liver injury is associated with increased reactive oxygen species (ROS) production, inflammatory factor secretion, and hepatocyte apoptosis 9,11 . Human fetal hepatocyte line, L02, has the advantage of excellent proliferative capacity and exhibits good liver function in vitro and in an ALF model 12 .…”

“…Animal model studies have shown that LPS‐induced liver injury is associated with increased reactive oxygen species (ROS) production, inflammatory factor secretion, and hepatocyte apoptosis. 9 , 11 Human fetal hepatocyte line, L02, has the advantage of excellent proliferative capacity and exhibits good liver function in vitro and in an ALF model. 12 Moreover, LPS induced L02 cell inflammatory injury has been widely used to study ALF in vitro.…”