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Mesenchymal stromal cells and liver fibrosis: a complicated relationship
Author(s) -
Haldar Debashis,
Henderson Neil C.,
Hirschfield Gideon,
Newsome Philip N.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600433r
Subject(s) - mesenchymal stem cell , medicine , fibrosis , stromal cell , cirrhosis , context (archaeology) , hepatic stellate cell , cell therapy , cancer research , immunology , bioinformatics , pathology , cell , biology , paleontology , genetics
Mesenchymal stromal cell (MSC) therapy demands the attention of clinicians and scientists because of its potential in clinical fields that are bereft of medical options, but also because of the controversies that underlie its mode of action. MSCs are potent immune modulators, yet their biologic activity may not be innate, requiring licensingbytheir micro environment. This property has promptedresearchers toexplore uniquewaysin whichMSCs may be able to exert distinct biologic effects in different pathologic settings. More than 400 clinical trials have investigated the therapeutic capacity of MSCs in different pathologies, including liver disease. Along with their antiinflammatory action, there are data to suggest thatMSCsmay exertdirect antifibrotic effects, although enthusiasm for their use in patients has been tempered by concerns of a possible profibrotic role of endogenousMSCsin response to injury. There is a significant need for antifibrotic therapy to combat the increasing burden of patientswith cirrhosis, and a concerted effort is required to determine the mechanisms by which MSCs modulate the liver's response to injury, both endogenously and after adoptive transfer. This review critically appraises the preclinical published data with regard to the capacity of MSCs to influence fibrotic response to liver injury and will explore the potential mechanisms that underpin the reportedbeneficial effects of MSCtherapy in the context of liver injury and fibrosis.—Haldar, D., Henderson, N. C., Hirschfield, G., Newsome, P. N. Mesenchymal stromal cells and liver fibrosis: a complicated relationship. FASEB J. 30, 3905–3928 (2016). www.fasebj.org