Mesenchymal Stromal Cells, a New Player in Reducing Complications From Liver Transplantation?

Abstract

In response to the global burden of liver disease there has been a commensurate increase in the demand for liver transplantation. However, due to a paucity of donor organs many centers have moved toward the routine use of marginal allografts, which can be associated with a greater risk of complications and poorer clinical outcomes. Mesenchymal stromal cells (MSC) are a multi-potent progenitor cell population that have been utilized to modulate aberrant immune responses in acute and chronic inflammatory conditions. MSC exert an immunomodulatory effect on innate and adaptive immune systems through the release of both paracrine soluble factors and extracellular vesicles. Through these routes MSC can switch the regulatory function of the immune system through effects on macrophages and T regulatory cells enabling a switch of phenotype from injury to restoration. A key benefit seems to be their ability to tailor their response to the inflammatory environment without compromising the host ability to fight infection. With over 200 clinical trials registered to examine MSC therapy in liver disease and an increasing number of trials of MSC therapy in solid organ transplant recipients, there is increasing consideration for their use in liver transplantation. In this review we critically appraise the potential role of MSC therapy in the context of liver transplantation, including their ability to modulate reperfusion injury, their role in the reduction of medium term complications in the biliary tree and their potential to enhance tolerance in transplanted organs.

Exosomes: Potential executors of IL‐35 gene‐modified adipose‐derived mesenchymal stem cells in inhibiting acute rejection after heart transplantation

“…How to establish immune tolerance to avoid the complications caused by long-term use of immunosuppressants has become the ultimate goal in the field of transplantation. In many explorations, MSC-based therapy has attracted increasing attention in solid organ transplantation, [21][22][23][24] especially genetic modification, which has enhanced the therapeutic effects of MSCs and greatly expanded their therapeutic prospects. [25][26][27] However, accumulating evidence suggests that MSCs exert their therapeutic effects, which is mainly attributed to their ability to interact with injured tissues by releasing soluble bioactive factors (ie paracrine function), rather than long-term integration into host tissues.…”

Organoid transplant approaches for the liver

“…Shortly after that, this technique was suggested for the treatment of liver cirrhosis and fibrosis. MSCs in the range of 10 5 -10 9 are infused by intravenous, intrahepatic, or intrasplenic injection; however, it is unclear whether this therapy contributes to liver regeneration in the long period [32,33]. In 2017, MSC Tx was reported to treat liver graft rejection; it was found that liver functions and allograft histology were improved in addition to Treg/Th17 ratio, CD4 + Tcell activation [34].…”

Role of the Microenvironment in Mesenchymal Stem Cell-Based Strategies for Treating Human Liver Diseases

“…Besides, the liver comprises parenchymal cells, such as hepatocytes, cholangiocytes, and LSPCs, as well as nonparenchymal cells, such as HSCs, LSECs, KCs, and other immune cells, both of which can present antigens as well as secrete cytokine and chemokine, thereby initiating immune responses [35][36][37].…”