The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma

Abstract

Primary liver cancer is the seventh most common cancer and the second most common cause of cancer death in the world. 1 Globally, hepatocellular carcinoma (HCC) is the main histological type of liver cancer, accounting for more than 75% of the total number of liver cancers. 2 Liver cancer stem cells (LCSCs), recognized by certain surface markers, are responsible for the tumorigenesis, recurrence, metastasis, chemotherapy resistance and poor prognosis of HCC. 3 Increasing evidence supports the great effects of the tumor microenvironment (TME) on the generation, development and metastasis of HCC. TME is composed of diversified cells and non-cellular components. 4 Mesenchymal stem cells (MSCs), an integral part of TME, are considered to be a key factor in tumor progression and metastasis. MSCs are also referred to as "mesenchymal stromal cells", which can further be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and other cells in vitro. 5 Recently, massive research has been devoted to exploring the association between HCC and MSCs. The function of

Structural and Temporal Dynamics of Mesenchymal Stem Cells in Liver Diseases From 2001 to 2021: A Bibliometric Analysis

“…Long-term liver fibrosis can promote the abnormal proliferation, regeneration and repair of hepatocytes, making hepatocytes prone to spontaneous mutations, thus developing into hepatocellular carcinoma (HCC). In this process, MSCs, as a part of the fibrosis inflammatory microenvironment matrix, may be involved in the initiation and progression of HCC ( 109 , 110 ). In the initial stage of HCC (Is), MSCs showed protective effects against drug damage by reducing DNA damage and ROS accumulation.…”

The origins, roles and therapies of cancer associated fibroblast in liver cancer

“…MSCs exhibit different characteristics such as suppressing and promoting tumors during the progression of HCC, therefore, their participation in HCC is controversial. It is believed that MSCs could have tumor suppressing effects in the initial stage of disease by reducing DNA damages, but in the later stage of HCC, MSC played a more tumor-promoting role by enhancing stem cell-like properties and promoting EMT ( 20 , 21 ). Chemotaxis signals secreted in fibrotic liver or tumor induce the homing properties of MSCs not only from adjacent tissues within the liver, but also from distant sites such as bone marrow ( 21 ).…”

“…It is believed that MSCs could have tumor suppressing effects in the initial stage of disease by reducing DNA damages, but in the later stage of HCC, MSC played a more tumor-promoting role by enhancing stem cell-like properties and promoting EMT ( 20 , 21 ). Chemotaxis signals secreted in fibrotic liver or tumor induce the homing properties of MSCs not only from adjacent tissues within the liver, but also from distant sites such as bone marrow ( 21 ). The “homing” ability of MSCs to injured tissue further initiate the malignant transformation of HCC ( 22 ).…”

Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy

“…Various chemotherapeutic agents, including doxorubicin (DOX), mitoxantrone, gemcitabine, irinotecan, sorafenib, etc., used both as single or as combinational agents, are available for the treatment of HCC [ 3 , 4 ]. Furthermore, a number of novel therapeutic strategies, such as treatments targeting cancer stem cells, molecular targeted therapy, and immunotherapy, are going to be developed [ 5 , 6 ]. However, poor prognosis is found in the majority of patients with HCC due to characteristics intrinsic to the tumor (in particular drug resistance) and mainly due to poor drug bioavailability, non-selective biodistribution, low specificity, and systemic toxicity.…”