Protective Effect Of Bone Marrow Mesenchymal Stem Cells And Their Apoptotic Bodies In Fetal Mice Caused By Cyclophosphamide

For a long time,chemical congenital developmental defects caused by chemical agents and drugs have received much attention.Many patients are difficult to cure or even lifethreatening,even if they spend a lot of money on treatment.Cyclophosphamide(CP)is a commonly used drug for the treatment of neoplastic diseases and autoimmune diseases.It is also a well-studied source of teratogenicity.Bone marrow derived mesenchymal stem cells(BMSCs)can be used for the treatment of tissue regeneration and autoimmune diseases,demonstrating a powerful immune regulation function.Other studies have shown that the bone marrow microenvironment,especially bone marrow mesenchymal stem cells,is essential for maintaining immune balance.The organelles in the apoptosis bodys(ABs)are surrounded by cell membranes,and there is no leakage of cellular contents,and the characteristic that does not cause peripheral inflammatory reactions exhibit the potential for treating fetal malformations.Studies have shown that apoptotic bodies play an important role in maintaining homeostasis and regulating immune function.We successfully constructed a mouse fetal malformation model by intraperitoneal injection of 20 mg/kg cyclophosphamide in mice 11.5 days pregnant(Embryo,E11.5).Subsequently,the teratogenic effects of cyclophosphamide on fetal rats were successfully prevented by intravenous injection of bone marrow mesenchymal stem cells and apoptotic bodies,respectively.By detecting the serum concentration of pregnant mice,we found that the concentration of cyclophosphamide metabolites was effectively reduced by bone marrow mesenchymal stem cells and apoptotic bodies.Through research,we found that the object of bone marrow mesenchymal stem cells and apoptotic bodies is the pregnant mice themselves.We found the bone marrow mesenchymal stem cells and apoptotic bodies in the liver of pregnant mice after injection.In further studies,we learned that Kupffer cells(KCs)in the liver can phagocytose exogenous bone marrow mesenchymal stem cells and apoptotic bodies.After injecting of cyclophosphamide into pregnant mice,the expression levels of tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and IL-18 secreted by Kupffer cells in the liver were up-regulated,while after phagocytosis of bone marrow mesenchymal stem cells and apoptotic bodies,the secretion of Kupffer cells(KCs)’s cytokines returned to normal levels.The expression level of cytokines is related to the activation of the NF-κB signaling pathway.By detecting the NF-κB signaling pathway in the immune-related pathway,we found that injection of cyclophosphamide up-regulated the expression levels of NF-κB signaling pathway-related proteins P65 and IκBα,while injection of bone marrow mesenchymal stem cells and apoptotic bodies P65 makes the expression level of IκBα returned to normal.This experiment demonstrates that exogenous bone marrow mesenchymal stem cells and apoptotic bodies can protect mouse fetus from the teratogenic effects of cyclophosphamide.