Liver disease and cell therapy - advances made and remaining challenges

The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant strides have been made in exploring their biological activity. Clinical application of MSC has shifted the paradigm from using their regenerative potential to one which harnesses their immunomodulatory properties. Reassuringly, MSCs have been extensively investigated for over 30 years with encouraging efficacy and safety data from translational and early phase clinical studies, but questions remain about their utility. Therefore, in this review we examine the translational and clinical studies using MSCs in various liver diseases and their impact on dampening immune-mediated liver damage. Our key observations include progress made thus far with use of MSCs for clinical use, inconsistency in the literature to allow meaningful comparison between different studies and need for standardised protocols for MSC manufacture and administration. In addition, the emerging role of MSC derived extracellular vesicles as an alternative to MSC has been reviewed. We have also highlighted some of the remaining clinical challenges that should be addressed before MSC can progress to be considered as therapy for patients with liver disease.