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Table 1 Studies on anti-fibrosis treatment related to ECM-degrading cells

From: Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy

Cell

Treatment

Mechanism

Application

Dose

Animal model

Injection method

Ref

Liver sinusoidal endothelial cells

Treatment with PMA and accutase

Increased expression of MMP1, MMP2, MMP9, etc

Advanced liver fibrosis

4 × 105

6-week-old nude mice, CCl4 induced liver fibrosis

Intrasplenic injection

Zhao et al. 2022

MSCs

Treatment with TNF-α

Increased expression of Mmp13

Pulmonary fibrosis

1 × 105

8 to 12-week-old C57BL/6 J mice, bleomycin-induced lung injury

Intratracheal injection

Wong et al. 2022

Bone MSCs

Overexpression of Smad7

Increased expression of MMP1

Liver cirrhosis

(3~5) × 106

6-week-old Wistar rats, CCl4 induced liver fibrosis

Intrahepatic injection

Su et al. 2020

Clonal mesenchymal stem cells

-

Increased expression of MMP2 and MMP9

Liver fibrosis

3 × 107

6-week-old Wistar rats, CCl4 induced liver fibrosis

Intrasplenic injection

Hardjo et al. 2009

MSCs

Combination therapy with serelaxin

Increased expression of MMP2 in kidney

Renal fibrosis

1 × 106

Male C57BL/6 J mice, unilateral ureteral obstruction induced renal fibrosis

Renal vein injection

Huuskes et al. 2015

Bone marrow mesenchymal stromal cells

-

Increased expression of MMP13 in M2 macrophage

Liver fibrosis

5 × 105

10-week-old C57BL/6 J male mice, CCl4 induced liver fibrosis

Tail vein injection

Luo et al. 2019

Human amnion epithelial cells

-

Downregulation of TIMP1, 2, 3, 4 in lung

Pulmonary fibrosis

1 × 106

8-week-old SCID mice, bleomycin induced pulmonary fibrosis

Tail vein injection

Moodley et al. 2010

Adipose-derived stem cells

 

Increased expression of MMP9 in liver

Liver fibrosis

1 × 106

8-week-old male Wistar rats, TAA induced liver fibrosis

Intrahepatic injection

Harn et al. 2012

Kupffer cells

-

Increased expression of MMP9

Liver fibrosis

2 × 106

C57BL/6 mice, TAA induced liver fibrosis

Intravenous injection

Feng et al. 2018

MSCs

Overexpression of hepatocyte growth factor (HGF)

Increased expression of MMP9, 13, 14 and uPA, decreased expression of TIMP1 in liver

Liver fibrosis

1 × 107

5-week-old Sprague–Dawley (SD) male rats, DMN induced liver fibrosis

Intrasplenic injection

Kim et al. 2014

Bone marrow-derived liver stem cells

Overexpression of uPA

Activation of pro-MMP3 by uPA, which activates MMP2 and MMP9, then degrading collagen

Liver fibrosis

2 × 106

Female F344 rats, CCl4 induced liver fibrosis

Tail vein injection

Sun et al. 2008

Bone marrow-derived MSCs

Treatment with IC-2

Increased expression of MMP1, MMP2, and MMP14

Liver fibrosis

-

7–9-week-old BALB/c-nu/nu male mice, CCl4 induced liver fibrosis

Intrahepatic transplantation

Itaba et al. 2019

Bone marrow‑derived MSCs

Transfection with survivin

Increased expression of MMP9 in lung

Pulmonary fibrosis

1 × 106

6–8-week-old C57BL/6 male mice, bleomycin induced pulmonary fibrosis

Caudal vein injection

Zhou et al. 2015

Induced pluripotent stem cells

-

Inhibition of imbalance in the expression ratios of MMP2/TIMP2 and MMP9/TIMP1

Pulmonary fibrosis

2 × 106

C57BL/6 male mice, bleomycin-induced pulmonary fibrosis

Intravenous injection

Zhou et al. 2016

Bone marrow MSCs

-

Increased expression of MMPs

Liver fibrosis

1 × 106

Adult male Wistar Kyoto (WKY) rats, CCl4 induced liver fibrosis

Portal vein injection

Zhao et al. 2012

Endometrial regenerative cells

-

Increased expression of MMP9

Pulmonary fibrosis

1 × 106

6–8-week-old C57BL/6 female mice, bleomycin-induced pulmonary fibrosis

Tail vein injection

Zhao et al. 2018

Bone-marrow-derived macrophages

Treatment with lipopolysaccharide (M1-polarized)

Increased expression of MMP2, 9, and 13 in recruited Ly6Clo macrophages

Liver fibrosis

1 × 106

8-week-old C57BL/6 male mice, CCl4 induced liver fibrosis

Tail vein injection

Ma et al. 2017

Bone marrow cells

-

Increased expression of MMP13 and MMP9 in some of bone marrow-derived cells and liver resident cells

Liver fibrosis

5 × 106

6-week-old C57BL/6 mice, CCl4 induced liver fibrosis

Intravenous injection

Higashiyama et al. 2007

Bone marrow-derived MSCs

-

Increased expression of MMP2 in liver

Liver fibrosis

3 × 106

Male Wistar rats, BDL induced liver fibrosis

Tail vein injection

Mohamed et al. 2016

Chorionic plate-derived MSCs

-

Increased expression of MMP9 in liver

Liver fibrosis

2 × 106

6-week-old male Sprague–Dawley rats, CCl4 induced liver fibrosis

Intrahepatic transplantation

Lee et al. 2010

Adipose-derived MSCs

-

Enhanced ratio of Mmp1/Timp1 in skin and lung tissues

Systemic sclerosis

2.5 × 105

C57BL/6 mice, hypochlorite (HOCl) induced systemic sclerosis

Tail vein injection

Maria et al. 2016

Bone marrow-derived MSCs

-

Enhanced ratio of MMP/TIMP production by cardiac fibroblasts

Cardiac ventricular fibrosis

3 × 106

Lewis congenic rats, interventricular artery ligation induced myocardial infarction

Intramyocardial injection

Mias et al. 2009