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.
Highlights
The global burden of liver pathology is often underestimated due to limitations in mortality recording systems in many countries [1], it is still estimated that over 2 million liverrelated deaths occur worldwide [2]
Mesenchymal stromal cells (MSC) may offer a novel cell therapeutic approach to impact on these negative squeal and potentially allow for expansion of the donor pool
THERAPEUTIC STRATEGIES UTILIZING MSC IN LIVER TRANSPLANTATION. Through their ability to reduce injury and cell death in models of ischemia and reperfusion injury it stands to reason that there is a role for MSC therapy in orthotopic liver transplantation (OLT)
Summary
The global burden of liver pathology is often underestimated due to limitations in mortality recording systems in many countries [1], it is still estimated that over 2 million liverrelated deaths occur worldwide [2]. The engraftment and function of these cells appears to show benefit in animal models of bone marrow MSC [93,94,95], there are conflicting results from pre-clinical studies rendering this a controversial area still requiring considerable attention before becoming a translatable therapy [96] Through their ability to reduce injury and cell death in models of ischemia and reperfusion injury it stands to reason that there is a role for MSC therapy in orthotopic liver transplantation (OLT). In small animal models of cardiac and renal transplant allogeneic bone marrow MSC are able to induce organ tolerance by down-regulating T lymphocyte responses through expression of indolamine 2,3dioxygenase [127, 128] In rats, both recipient and donor derived bone marrow MSC prolonged survival of transplanted livers through induction of FoxP3 T regulatory cells [125]. Long term in vitro studies of murine bone marrow MSC have demonstrated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
