Use of Neuroglial Antigen 2 (NG2)-Expressing Mesenchymal Stem-Like Cells for Liver Fibrosis/Cirrhosis: A New Scene

End-stage liver disease (ESLD) and liver failure are major health problems worldwide, leading to high mortality, morbidity, and healthcare costs. Currently, orthotropic liver transplantation (LTx) is the only effective treatment for the disease. However, a shortage of donors limits treatment for patients with ESLD. Stem cell therapy has provided a valuable adjunct to LTx and has immense potential in the management of ESLD. Among immense therapies using stem cells, for example, bone marrow-derived mesenchymal stem cells (BmMSCs), they have emerged in the field either as a direct contribution to functional hepatic differentiation or as seed cells in acellular three-dimensional (3D) liver scaffolds (3D-DLSs) for functional liver tissue construction. BmMSC infusion in cirrhotic patients has improved liver parameters and could form a viable bridge to LTx. Despite prominent advantages, the BmMSCs have encountered frustrating challenges, a heterogeneity problem, which has been the central dilemma impairing their clinical application. The present chapter provides a comprehensive outlook on how this drawback could led to current challenges in the field and demonstrates several potentially viable options to address these challenges. Herein, we introduced a novel proliferated subpopulation in of BmMSCs that express neuron-glial antigen 2 (NG2), a classical stem cell marker in the central nervous system (CNS) that can be isolated using a unique protocol, the Percoll-plate-wait procedure. This chapter also provides a detailed protocol for obtaining NG2-expressing cells (NG2+ cells) from heterogenous BmMSC cultures (namely, NG2+/BmMSCs), liver-derived NG2+ cells (namely MLpvNG2+ cells), and comparisons of NG2+/BmMSCs with MLpvNG2+ cells and parental BmMSCs. Reviewing relevant studies in the field and combined with our recent experimental analysis, this chapter summarizes the basic characteristics of NG2+/BmMSCs biology relevant to advances over BmMSCs regarding the possibility of using stem cells for ESLD by enhancing efficacy and reconstructing biliary tree and hepatic blood sinusoidal anatomical structures for transplantable large-scale liver tissues to replace failed liver.