Mesenchymal stromal cells and liver fibrosis: a complicated relationship

Abstract

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 licensing by their microenvironment. This property has prompted researchers to explore unique ways in which MSCs 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 anti-inflammatory action, there are data to suggest that MSCs may exert direct antifibrotic effects, although enthusiasm for their use in patients has been tempered by concerns of a possible profibrotic role of endogenous MSCs in response to injury. There is a significant need for antifibrotic therapy to combat the increasing burden of patients with 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 reported beneficial effects of MSC therapy 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.

Mesenchymal stromal cells prevent bleomycin‐induced lung and skin fibrosis in aged mice and restore wound healing

“…Also, combination therapies may be less effective given the potential of additive side effects. Cell‐based therapies, such as ASCs, have been studied as anti‐fibrotic therapy in several organs (Chen et al, ; Glassberg et al, ; Haldar et al, ; Otero‐Vinas & Falanga, ; Wang et al, ). ASCs appear to act by paracrine effects to modulate multiple pathways and demonstrate an ability to adapt to the local tissue to restore homeostasis and promote tissue repair (Usunier et al, ).…”

“…MSCs have been shown to exert anti‐inflammatory, anti‐oxidant, and immunomodulatory effects, as well as an ability to modulate pro‐fibrotic factors (Eming, Martin, & Tomic‐Canic, ; Toonkel, Hare, Matthay, & Glassberg, ; Usunier et al, ). MSCs have been investigated in pre‐clinical and clinical studies for diseases in various organs including the heart (Chen et al, ), lung (Glassberg et al, ), kidney (Wang et al, ), liver (Haldar, Henderson, Hirschfield, & Newsome, ), and skin (Ojeh, Pastar, Tomic‐Canic, & Stojadinovic, ; Otero‐Vinas & Falanga, ). Benefits of MSCs in various organs are thought to stem from their ability to adapt to the local environment and regulate its secretome (Usunier et al, ).…”

Células tronco mesenquimais derivadas de tecido adiposo no tratamento de cirrose hepática

“…Para o tratamento de hepatopatias, as células tronco derivadas de medula óssea (BM-MSC) foram largamente testadas em modelos animais e ensaios clínicos apresentando relativo sucesso (ANDREONE et al, 2015;HALDAR et al, 2016;LI et al, 2015;MOHAMADNEJAD et al, 2016). No entanto, essas células são de difícil obtenção devido a procedimentos dolorosos e os rendimentos são relativamente baixos (WP, 2015;ZUK, 2010).…”

Milk Fat Globule-EGF Factor 8 for Liver Fibrosis Therapy: Creaming Off the Beneficial Effects of Mesenchymal Stromal Cells

“…1 These include endothelial progenitor cells, 2 macrophages, 3 and various types of mesenchymal stromal cells (MSCs). 4 The latter cell types have been the most widely tested in both preclinical models of liver fibrosis and in clinical trials of MSC therapy for liver cirrhosis. 5 The MSCs are attractive cells to use because they can be readily grown in vitro from various sources, including bone marrow, fat, and umbilical cord.…”

“…6,7 Furthermore, MSCs have a multiplicity of effects that likely vary according to both their local environment and phase of liver injury, namely, formation or resolution of fibrosis. 4 Given the complex nature of MSCs, 1 option would be to identify their specific antifibrotic factors and therefore develop more targeted therapy, using the effector molecules themselves, thus avoiding the need for cell injections altogether. Along this line, the potential antifibrotic effects of human cord blood MSC exosomes was shown in a mouse model of liver fibrosis where a single injection of the exosomes reduced fibrosis.…”