Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases

Abstract

Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.

Keywords: Acquired; Advanced liver diseases; Intrinsic; Stem cell; Therapeutic strategy.

Fig. 1

One produced two, two produced three, and three produced all things. Stem cells harbor self-renewal and differentiation abilities, which enable such cells to maintain the cell population and form functional units, thus leading to the future of providing all patients with appropriate newborn livers.

Fig. 2

Potential intrinsic and acquired stem cell therapy. There are two stem cell therapies for advanced liver diseases, intrinsic and acquired, to treat the patients possibly. As for the former, the upregulation of Hippo-YAP, Notch and uncanonical Wnt pathways promote the expansion of BECs, then the downregulation of Notch-Sox9b pathways proceeds dedifferentiation of BEC, and at last, upregulation of BMP-tbx2b and canonical Wnt pathways and downregulation of EGFR-ERK-sox9 pathway assist the process of LPC-to-hepatocytes. In contrast, the role of the PI3K-AKT-mTORC1 pathway remains unclear. Cell sources for acquired stem cell therapy in advanced liver diseases include fetal-related tissue and adult tissue, from which mesenchymal and fetal stem cells can be isolated and induced pluripotent stem cells can be reprogrammed. For their application, there are indirect and direct approaches. On the one hand, these cells are cultured into hepatocyte-like cells consequent to the differentiation in vitro. Contrarily, MSC and FSC can use in the patient directly since they could differentiate in vivo with relatively low risk. iPSC, induced pluripotent stem cell; MSC, mesenchymal stem cell; FLSC, fetal liver stem cell; BEC, biliary epithelial cell; LPC, liver progenitor cell.