A Proposed Novel Stem Cell Therapy Protocol for Liver Cirrhosis

Abstract

Currently, there is not an effective therapy for cirrhosis of the liver except for liver transplant. However, finding a compatible liver is difficult due to the low supply and increased demand for healthy livers. Stem cell therapy may be a solution for liver cirrhosis. In our previous report, stem cells from Wharton's jelly and bone marrow were shown to improve liver function in a chemically induced liver fibrosis animal model. However, the immunological rejection of an allograft is always a risk for clinical application. In this study proposal, we suggest using human adipose-derived stem cells (ADSCs) because they are an immune-privileged cell type; they lack human leukocyte antigen-DR expression, and they also suppress the proliferation of activated allogenic lymphocytes and inhibit the production of inflammatory cytokines. In addition, ADSCs contain a sufficient amount of adult stem cells for autologous transplantation. Based on these benefits, ADSCs are promising candidates for clinical application when compared to other stem cell types. The aim of our study will be to investigate the safety and efficacy of autologous ADSCs for the clinical treatment of liver cirrhosis.

Zebularine Promotes Hepatic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells by Interfering with p38 MAPK Signaling

“…Therefore, the derivation of hepatocytes from stem cells is of value in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Nowadays, autologous BMMSCs have been widely applied in the liver repair, but its efficacy is often limited by the low transdifferentiation rate [ 21 – 23 ]. Cytokines, including HGF, epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) 165 [ 11 ], have been shown to induce hepatic differentiation of BMMSCs, though their application is limited by short half-life in vivo and hemodynamic abnormalities and potentially severe side effects when used in large doses.…”

Commercial Production of Autologous Stem Cells and Their Therapeutic Potential for Liver Cirrhosis

“…Even with this increased yield, the demand for ADSCs generally exceeds their availability for personalized therapy. The current stem cell transplantation dosage for clinical use is 1 × 10 8 ADSCs 24–26 . According to the report by Lin et al 17 , 20 kg of fat tissue is needed to isolate this number of ADSCs.…”

Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) Regulates the Expression of B-Cell Lymphoma/Leukemia-2 (Bcl-2) and Promotes the Survival of Mesenchymal Stem Cells (MSCs) via PGC-1α/ERRα Interaction in the Absence of Serum, Hypoxia, and High Glucose Conditions

“…First, MSCs will differentiate into vascular cells, such as vascular smooth muscle cells and vascular endothelial cells, and directly generate new blood vessels. Second, MSCs will secrete many growth factors, such as vascular endothelial cell growth factor and basic fibroblast growth factor, and indirectly promote the formation of new blood vessels [20–22]. …”