Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough

Table 9

Summary of various in vitro studies using MSC-conditioned medium or MSCs cocultured with cells of interest.

References	Culture conditions	Cell type	MSC source	Outcome
[44]	MSC-conditioned medium	Cardiac fibroblasts	BM	(i) Reduced collagens I and III deposit; (ii) Decreased viability; (iii) Decreased expression of α-SMA; (iv) Increased of MMP-2 and MMP-9 activity; (v) Increased expression of MT1-MMP; (vi) Decreased expression of TIMP-2; MMP-2 −/− MSC-conditioned medium: (i) No change in collagen concentration; Incubation with anti-HGF antibody: (i) Reduced MMP-2 and MMP-9 activity; (ii) Decreased expression of MMP-2; (iii) Increased expression of TIMP-2
[64]	MSC-conditioned medium	TGF-β1-treated HK2	BM	(i) Decreased concentration of α-SMA; (ii) Increased concentration of E-cadherin
[51]	Coculture: MSCs	Fibrotic hepatocytes	BM	Increased secretion of FGF2
[73]	Coculture: MSCs in Transwell	HPMCs	BM	(i) Decreased expression of TGF-β1; (ii) Decreased expression of fibronectin; (iii) Decreased concentration of pSmad2; (iv) Decreased expression of α-SMA
[77]	Coculture LPS + IFN-γ-treated MSCs	Activated macrophages	BM	(i) Reduced concentration of TNF-α and IL-12; (ii) Reduced concentration of NO
[62]	MSCs in Transwell; Pretreatment of one or both cell types with HSA	PTECs	BM	(i) Reduced expression of TNF-α, IL-6, IL-8, MCP-1, and CCL-5; (ii) Inhibition of NF-κB nuclear translocation; (iii) Reduced EMT; (iv) Increased expression and concentration of HGF and TSG-6 by MSCs exposed to HSA; (v) Recombinant HGF or TSG-6 partially reproduces MSCs'effects

Influence of culture conditions on the outcome. Outcomes are expressed compared to control groups (i.e., groups treated without the use of MSC treatment) unless stated otherwise (α-SMA: α-smooth muscle actin; BM: bone marrow; CCL: chemokine ligand; EMT: epithelial-to-mesenchymal transition; FGF: fibroblast growth factor; HGF: hepatocyte growth factor; HK2: human kidney 2; HPMC: human peritoneal mesothelial cells; HAS: human serum albumin; HGF: hepatocyte growth factor; IFN-γ: interferon-γ; IL: interleukin; LPS: lipopolysaccharide; MCP: monocyte chemoattractant protein; MMP: matrix metalloproteinase; MSC: mesenchymal stromal cell; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B-cells; NO: nitric oxide; proximal tubular epithelial cell; pSmad: phosphorylated small mothers against decapentaplegic homolog; TGF-β: transforming growth factor-β; TIMP: tissue inhibitor of metalloproteinase; TNF-α: tumor necrosis factor-α; TSG-6: TNF-stimulated gene 6).