Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough

Table 3

MSC treatment on preclinical kidney fibrosis models.

References	Organism	Model	Treatment	MSC source	Timing	Quantity	Route	Outcome
[60]	Mouse	R-UUO	10 days UUO	BM	10 days after UUO	10^6 cells	Renal artery	(i) Decreased expression of TNF-α, TGF-β1, and α-SMA; (ii) Increased expression of E-cadherin
[61]	Pig	ARAS	Irritant coil placed in the main renal artery	AT	6 weeks after ARAS	10^6 cells	Local	(i) Reduced fibrotic area; (ii) Reduced number of CD163 + macrophages; (iii) Increased number of regulatory macrophages; (iv) Increased expression of IL-10; (v) Decreased expression of TNF-α; (vi) Reduced concentration of MMP-2; (vii) Increased expression of VEGF, FLK-1, and HIF1-α; (viii) Reduced MCP-1 positive area
[62]	Rat	Albumin-overload + uninephrectomy	Nephrectomy followed by 5 intraperitoneal injections of BSA (10 mg/g) per weeks during 4 weeks	BM	7 days after the first BSA injection	10^6 cells weekly for 4 weeks	IV	(i) Reduced expression and concentration of MCP-1 and CCL-5; (ii) Reduced expression and concentration of α-SMA; (iii) Reduced expression and concentration of collagen IV
[63]	Rat	Allograft	Bi-nephrectomization and single kidney allograft	BM (melatonin treated)	11 weeks after graft	5.10^5 cells	Tail vein	(i) Decreased expression of IL-6, IL-7r, IL-23a, and IL-10; (ii) Decreased concentration of CTGF and α-SMA; (iii) Decreased expression of fibronectin; (iv) Decreased expression of bFGF
[64]	Rat	NIRC	Excision of the right kidney, 45-minutes ischemia in the left kidney followed by 28-day cyclosporine A treatment	BM	7 or 14 days after ischemia-reperfusion	3.10^6 cells	Local	MSC transplantation 7 days after ischemia reperfusion: (i) Decreased fibrotic area; (ii) Decreased expression of collagen types I, III, and IV; (iii) Reduced number of α-SMA-positive cells; (iv) Decreased activity of MMP-2 (sham level); MSC transplantation 14 days after ischemia reperfusion showed no significant improvement
[65]	Rat	RKM	5/6 nephrectomy	BM	2 weeks after surgical procedure	−2.10^5 cells or −2.10^5 cells every other week (weeks 2, 4, and 6)	IV	(i) Reduced fibrotic area; (ii) Increased expression of IL-4 and IL-10; (iii) Decreased expression of IL-6 and TNF-α; (iv) Decreased expression of TGF-β1, Smad3, α-SMA, FSP-1, and vimentin; (v) Decreased expression of collagen type I, collagen type III, fibronectin, and TIMP-1/MMP-9 ratio; (vi) Increased expression of HO-1; (vii) Decreased expression of MCP-1; (viii) Increased expression of HGF
[66]	Rat	UUO	1 to 4 weeks obstruction	BM	Prior to UUO	10^6 cells	Renal artery	(i) Decreased collagen concentration; (ii) Decreased expression of TNF-α; (iii) Decreased concentration of TNF-α; (iv) Decreased expression of α-SMA; (v) Decreased number of FSP-1 positive cells; (vi) Increased expression of E-cadherin

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; ARAS: atherosclerotic renal artery stenosis; AT: adipose tissue; BSA: bovine serum albumin; CCL: chemokine ligand; CTGF: connective tissue growth factor; FGF: fibroblast growth factor; FLK: fetal liver kinase; FSP: fibroblast specific protein; HGF: hepatocyte growth factor; HIF: hypoxia-inducible factor; HO-1: heme oxygenase 1; IL: interleukin; IV: intravenous; MCP: monocyte chemoattractant protein; MMP: matrix metalloproteinase; MSC: mesenchymal stromal cell; NIRC: nephrectomy + ischemia-reperfusion + cyclosporine; R-UUO: reversible unilateral ureteral obstruction; TGF-β: transforming growth factor-β; TIMP: tissue inhibitor of metalloproteinase; TNF-α: tumor necrosis factor-α; UUO: unilateral ureteral obstruction; VEGF: vascular endothelial growth factor).