Therapeutic efficiency of bone marrow-derived mesenchymal stem cells for liver fibrosis: A systematic review of in vivo studies

Figure 1 Introduction of the main parts of the review. First, bone marrow-derived mesenchymal stem cells (BM-MSCs) are introduced as a therapy for liver fibrosis, then the steps before transplantation (culture, strategies, and the choice of transplantation route) are discussed. After that, the efficiency of BM-MSCs for liver fibrosis in vivo are explained through studies that research the efficiency, studies that compare the therapy to other medication sources, and the strategies to enhance the therapeutic efficiency.

Figure 2 The transition from a healthy liver to liver fibrosis. Different types of hepatotoxic agents produce mediators that induce inflammatory actions in hepatic cell types. Following chronic liver injury, symptoms associated with advanced hepatic fibrosis will appear. This can either lead to liver cirrhosis, liver failure, and portal hypertension or can be resolved under the conditions mentioned. HCV: Hepatitis C virus; LPS: Lipopolysaccharide.

Figure 3 Eminent sources of adult mesenchymal stem cells and the cells into which they can differentiate. Eminent sources of adult mesenchymal stem cells are ordered through their therapeutic eminence index. Umbilical cord is the most eminent, followed by the placenta, adipose tissue, endometrium, dental pulp, and dermis. The least eminent sources are amniotic fluid, synovium, and breast milk. The cell types, such as neurons, enterocytes, osteocytes, and chondrocytes, into which the isolated mesenchymal stem cells can differentiate are variant.

Figure 4 Bone marrow extracted cells. Bone marrow contains a variety of stem cell populations that can be extracted, either through specific growth factor media, such as that for multipotent adult progenitor cells (MAPCs) and mesenchymal stem cells (MSCs) or through flow cytometric cell sorting (FACS) technology, such as for the endothelial progenitor cells (EPCs), hematopoietic stem cells (HPSCs), and side population cells (SPs).

Figure 5 Potential contributions of bone marrow-derived mesenchymal stem cells to liver fibrosis. Each of the presented elements represent a distinct mechanism that has a specific role that can contribute to alleviating liver fibrosis. BM-MSCs: Bone marrow-derived mesenchymal stem cells; HSCs: Hepatic stellate cells; KC: Kupffer cells.

Figure 6 Two main types of mesenchymal stem cell culture. The two-dimensional (2D) culture using 2D dishes as a monolayer for fast expansion, and the three-dimensional (3D) culture with two main types of spheroid use: multiple cell-derived spheroid and single cell-derived sphere. MSCs: Mesenchymal stem cells.

Figure 7 Strategies to enhance bone marrow-derived mesenchymal stem cell therapeutic efficiency. Genetic engineering and preconditioning used during the culture phase; tissue engineering used on a three-dimensional (3D) matrix and involving signaling molecules; cell-free therapy through the use of exomes and microvesicles. MSCs: Mesenchymal stem cells.

Figure 8 Bone marrow-derived mesenchymal stem cell transplantation routes for liver disease. The routes are either direct (portal vein and hepatic artery) or indirect (peripheral vein, intrasplenic, intraperitoneal, bone marrow reconstitution, and extra-corporeal liver assist). BM-MSCs: Bone marrow-derived mesenchymal stem cells.