Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough

Table 7

MSC treatment on preclinical cutaneous fibrosis models.

References	Organism	Model	Treatment	MSC source	Timing	Quantity	Route	Outcome
[75]	Mouse	Bleomycin	Daily subcutaneous injection of 0.5, 1, 3, or 5 mg/mL bleomycin during 4 weeks	BM	3 hr after bleomycin injection	10^6 cells	Local	(i) Reduced number of macrophages and neutrophils; (ii) Decreased expression of TGF-β1; (iii) Reduced number of α-SMA-positive cells; (iv) Decreased expression of collagen type I; (v) Increased expression of MMP-2, MMP-9, and MMP-13
[76]	Mouse	Radiation-induced	35 grays irradiation	BM (autologous or allogenic)	6 weeks after irradiation	5.10^5 cells	Tail vein	(i) No difference between autologous and allogeneic cells; (ii) Reduced fibrotic area; (iii) Reduced number of CD68 positive cells and CD80 positive cells; (iv) Increased number of CD163 positive cells; (v) Modification of macrophages toward a regulatory phenotype; (vi) Increased expression of IL-10; (vii) Increased concentration of IL-10; (viii) Decreased expression of IL-1β and Serpine1; (ix) Decreased concentration of IL-1α, IL-1β, and TNF-α; (x) Increased expression of PDGF-a
[77]	Mouse	Surgery	Four 6 mm full-thickness wounds on the back	BM	24 hr after surgery	10^6 cells	Local (around the wound)	(i) Decreased concentration of TNF-α (sham level with TSG-6 silenced MSCs); (ii) Decreased secretion of TNF-α by macrophages (no change in the number of macrophages); (iii) TGF-β1 concentration: increased on day 2; decreased on day 5; sham level with TSG-6 silenced MSCs; (iv) Increased concentration of TGF-β3 (sham level with TSG-6 silenced MSCs); (v) Decreased α-SMA expression; (vi) Decreased concentration of collagens 1α1, 1α2, and 3α1

Influence of fibrosis induction methods, MSC source, timing of injection, quantity of MSCs transplanted, and transplantation route. Outcomes are expressed compared to control groups (i.e., groups treated but not transplanted with MSCs) unless stated otherwise (α-SMA: α-smooth muscle actin; BM: bone marrow; IL: interleukin; MMP: matrix metalloproteinase; MSC: mesenchymal stromal cell; PDGF: platelet-derived growth factor; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-α; TSG-6: TNF-stimulated gene 6).