Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Abstract

The liver, the largest organ with multiple synthetic and secretory functions in mammals, consists of hepatocytes, cholangiocytes, hepatic stellate cells (HSCs), sinusoidal endothelial cells, Kupffer cells (KCs), and immune cells, among others. Various causative factors, including viral infection, toxins, autoimmune defects, and genetic disorders, can impair liver function and result in chronic liver disease or acute liver failure. Mesenchymal stem cells (MSCs) from various tissues have emerged as a potential candidate for cell transplantation to promote liver regeneration. Adipose-derived MSCs (ADMSCs) with high multi-lineage potential and self-renewal capacity have attracted great attention as a promising means of liver regeneration. The abundance source and minimally invasive procedure required to obtain ADMSCs makes them superior to bone marrow-derived MSCs (BMMSCs). In this review, we comprehensively analyze landmark studies that address the isolation, proliferation, and hepatogenic differentiation of ADMSCs and summarize the therapeutic effects of ADMSCs in animal models of liver diseases. We also discuss key points related to improving the hepatic differentiation of ADMSCs via exposure of the cells to cytokines and growth factors (GFs), extracellular matrix (ECM), and various physical parameters in in vitro culture. The optimization of culturing methods and of the transplantation route will contribute to the further application of ADMSCs in liver regeneration and help improve the survival rate of patients with liver diseases. To this end, ADMSCs provide a potential strategy in the field of liver regeneration for treating acute or chronic liver injury, thus ensuring the availability of ADMSCs for research, trial, and clinical applications in various liver diseases in the future.

Sinusoidal endothelial cell progenitor cells promote tumor progression in the patients with hepatocellular carcinoma.

“…Previous studies have indicated that BM SEPCs drove the liver regeneration process. These BM SEPCs repaired lost or injured LSECs, leading to engraftment of a substantial number of BM SEPCs and BM-derived LSECs after injury or partial hepatectomy 11,13 . Recruitment of BM SEPCs to the liver occurred through activated signaling of VEGF-sdf1 and BM SEPCs provided most of the increase in LSEC-related HGF after injury, which further promoted hepatocyte proliferation and normal liver regeneration 8,12 .…”

“…Numerous of studies regarding liver regeneration have indicated that bone marrow (BM)-derived sinusoidal endothelial cell progenitor cells (BM SEPCs) drove the liver regeneration process. These BM SEPCs repaired lost or injured liver sinusoidal endothelial cells (LSECs), leading to engraftment of a substantial number of SEPCs and BM-derived LSECs through signaling by VEGF-stromal cell derived factor 1 (sdf1) after injury or partial hepatectomy [11][12][13][14][15] . The VEGF also stimulated increased HGF expression in the cells of the LSEC fraction, i.e., mature LSECs and/or SEPCs 12 .…”

The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy

“…With the above characteristics, MSCs are commonly used in cell therapy for regenerative medicine and immunotherapy (Squillaro et al, 2016;Galipeau and Sensebe, 2018). MSCT has caused increasing attention and is regarded as a potential new therapy for a variety of human diseases associated with brain, liver, kidney, bone, and so on (Hu et al, 2018;Chakari-Khiavi et al, 2019;Hu et al, 2019;Missoum, 2020). However, the direct use of MSCs for treating diseases encounters some problems.…”

Stem Cell Therapy

“…However, there is a shortage of suitable donor organs, and researchers are working on cell therapies in order to temporarily improve the liver's function, enabling the patient to survive longer time periods before transplantation with the final goal to replace liver transplantation altogether. The first completed trials which all employed some kind of MSC obtained, e.g., from autologous fat tissue or BM indicate an overall safety of the procedure with limited success (Hu et al 2019).…”