Mesenchymal stromal cells and liver fibrosis: a complicated relationship

Mesenchymal stromal cell (MSC) therapy demands the attention of clinicians and scientists due to its potential in clinical fields bereft of medical options, but also because of the controversies underlying its mode of action. MSC are potent immune-modulators, yet their biological activity may not be innate, requiring licencing by their microenvironment. This property has prompted researchers to explore unique ways in which MSC may be able to exert distinct biological effects in different pathological settings.

Over four hundred clinical trials have investigated the therapeutic capacity of MSC in different pathologies including liver disease. Alongside their anti-inflammatory action, there are data to suggest MSC may exert direct anti-fibrotic effects, although enthusiasm for their use in patients has been tempered by concerns of a possible pro-fibrotic role of endogenous MSC in response to injury. There is a significant need for anti-fibrotic therapy to combat the increasing burden of patients with cirrhosis, and a concerted effort is required to determine the mechanisms by which MSC modulate the liver’s response to injury, both endogenously and after adoptive transfer.

This review critically appraises the pre-clinical published data with regards to the capacity of MSC to influence the fibrotic response to liver injury, and will explore the potential mechanisms that underpin the reported beneficial effects of MSC therapy in the context of liver injury and fibrosis.