Mesenchymal Stem Cells Mitigate Cirrhosis through BMP7

Abstract

Background/Aims: Transplantation of mesenchymal stem cells (MSCs) has therapeutic effects on various diseases, while its effect on developing cirrhosis as well as the underlying mechanism remained largely unknown. Methods: Twenty C57BL/6 mice were randomly separated into 2 groups of ten each. One group received transplantation of MSCs, while the other group received saline as control. The mice then received intraperitoneal injection of carbon tetrachloride (CCl₄) twice per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure, sodium balance and excretion. Transcripts of transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the mouse livers were quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this model, and compared to MSCs. Results: Liver fibrosis, portal hypertension and sodium retention that were developed by CCl₄, were all significantly alleviated by MSCs transplantation, which decreased TGFβ1 levels and increased BMP7 levels in the injured liver. MSCs were found to express extremely high levels of BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of MSCs against CCl₄-induced cirrhosis. Conclusions: MSCs mitigate cirrhosis through their production of BMP7 against the fibrogenic effect of TGFβ1 in the injured liver.

Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury in Mice by MiR-142a-5p-Controlled Pulmonary Endothelial Cell Autophagy

“…Mesenchymal stem cells (MSCs) have been initially identified in the bone marrow, and are the stem-like cells that expand in culture and may differentiate into osteoblasts, chondrocytes, and adipocytes [8][9][10][11][12][13][14]. Clinical data provide evidence to demonstrate a therapeutic effect of transplantation of MSCs in some diseases, including ALI, in which MSCs promote tissue repair through various mechanisms [9][10][11][12][13][14].…”

“…Clinical data provide evidence to demonstrate a therapeutic effect of transplantation of MSCs in some diseases, including ALI, in which MSCs promote tissue repair through various mechanisms [9][10][11][12][13][14]. When MSCs are intravenously delivered, they are mainly localized in the lungs, as a privilege for them to be used for treating lung diseases [15].…”

Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury

“…Owing to the potential effects on tissue repair, transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) has been used in treating a variety of diseases [1-3], including spinal cord injury (SCI), in which the neural cell regeneration was compensated by MSC grafting [4-6]. …”

Suppression of MicroRNA-383 Enhances Therapeutic Potential of Human Bone-Marrow-Derived Mesenchymal Stem Cells in Treating Spinal Cord Injury via GDNF

“…Recently, MSCs have been shown to have significant therapeutic effects on a variety of diseases, since mesenchymal cells play a critical role in tissue repair and organ remodeling. For example, Li et al showed that transplantation of MSCs mitigates the severity of cirrhosis by secreting BMP7 to contradict the fibrogenic effects of transforming growth factor beta 1 (TGF-beta1) in the injured liver [5]. In another elegant study, transplantation of mesenchymal stem cells (MSCs) alleviated dextran sulfate sodium -induced colitis through their crosstalk with macrophages via TGF-beta receptor signaling [4].…”