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Table 1 Summary of evaluation of the efficacy of stem cells in treating renal fibrosis

From: Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis

Author, year Stem cell type Animal model Groups Handling methods Treatment effect
Ninichuk et al. 2006 [114] BM-MSCs COL4A3-deficient mouse (Alport disease model) Wild-type group (n = 6), Collagen4A3−/− + saline group (n = 10), Collagen4A3−/− + MSC group (n = 10) Injected with BM-MSCs (1 × 106) or vehicle via tail vein BUN↓, Scr↓, EVGF→, BMP7→, inhibit glomerulosclerosis and renal fibrosis
Asanuma et al. 2011 [110] AD-MSCs UUO rat Sham group; UUO group; UUO + AD-MSCs group Cells (1 × 106) were injected through the renal artery α-SMA↓, FSP+ cell ↓, TNF-α↓, total collagen content↓, E-cadherin↑, EVGF→, TGF-β1→, IL-10→, FGF→, HGF→, inhibit EMT and renal fibrosis
Donizetti-Oliveira et al. 2012 [117] AMSCs IRI mice Sham group; IR group; IR + AMSCs group Cells (2 × 105) were intraperitoneally administered to each mice IL-1α↓, IL-6 ↓, TNF-α↓, IL-4, IL-10↑, IL-12↓, HO-1↑, RANTES↓, FSP-1↓, Col-I↓, hypoxyprobe↓, KC→, IL-1β→, IL-13→, inhibit renal fibrosis
Du et al. 2012 [22] WJ-MSCs IRI rat (i) Normal rats (n = 8); (ii) sham-operated rats (n = 16); (iii) vehicle-injected IRI rats (n = 16); (iv) WJ-MSC-injected IRI rats (n = 16) Intravenous infusion of 2 × 106 WJ-MSCs Scr↓, BUN↓, p-Akt↑, HGF↑, HO-1↑, IL-10↑, collagen↓, α-SMA↓, renal fibrosis↓ renal tubular cell apoptosis↓, renal tubular cell proliferation↑
Sedrakyan et al. 2012 [118] AF-MSCs Transgenic Alport C57BL/6 mice (Col4a5 knockout mice) (1) Wild-type C57BL/6 mice (n = 15), (2) Col4a5−/− mice (n = 25), and (3) Col4a5−/− mice + mouse AFSC Cells (1 × 106) were injected into the left ventricle Col4a1↑, Col4a2↑, Col4a3↑, Col4a4↑, Col4a5↑, Col4a6→, glomerular and interstitial fibrosis↓
Du et al. 2013 [119] WJ-MSCs IRI rat (a) Sham group (n = 24); (b) unilateral IRI group (n = 24); (c) unilateral IRI plus MSC-injected group (n = 24); and (d) unilateral IRI plus nephrectomized group (n = 24) Intravenous infusion of 2 × 106 WJ-MSCs Total renal collagen concentration↓, E-cadherin↑, α-SMA↓, HGF/TGF↑, renal fibrosis↓
Huang et al. 2013 [120] uUC-MSCs UUO rat UUO group, n = 21; UUO + MSC group, n = 21; Sham group, n = 21; Sham + MSC group, n = 21 Injected with MSCs (5 × 106) or vehicle via tail vein Inhibit renal fibrosis
Katsuno et al. 2013 [121] AMSCs AKI rat model induced by folic acid Control group, AKI + hHASCs group, and AKI + hLASCs group Intravenous injection Scr→, BUN→, HGF→, VEGF→
Quimby et al. 2013 [122] AMSCs Cat CKD model Study 1 (six cats) received 2 × 106 cryopreserved aMSCs per infusion, study 2 (five cats) received 4 × 106 cryopreserved aMSCs per infusion, study 3 (five cats) received 4 × 106 aMSCs 4 ×  106 MSCs intravenously × 3 treatments Scr→, BUN→, IL-8→, MCP-1→, TGF-β1→, VEGF→
Sun et al. 2013 [123] AF-MSCs UUO mice Normal group, UUO group, UUO + hAFSCs group 3.5 × 105 MSCs were injected via tail vein HIF-1α↓, TGF-β1↓, Col-I↓, MCP-1↓, VEGF↑, E-cadherin↑, PCNA↑, Ki67↓, cell apoptosis↓, renal fibrosis↓
Zhou et al. 2013 [124] uUC-MSC exosome Cisplatin-induced AKI rat model Normal group; AKI group; AKI + hucMSC-ex group; AKI+ hucMSC-CM group; AKI + non-hucMSC-ex; group; HFL-1-ex group 200 μg hucMSC-ex was injected into the kidneys via the renal capsule 8-OHdG↓, GSH↑, MDA↓, caspase 3↓
Baulier et al. 2014 [125] AF-MSCs Kidney transplantation model induced with IRI (pig) The vehicle group, the AF-MSC group, the control group Cells (1 × 106) were injected into the renal artery of the grafted kidney Scr↓, proteinuria↓, α-SMA↓, VEGF-A↓, Ang 1, Flt-1↓, renal fibrosis↓
Iwai et al. 2014 [126] AMSCs Rat DCD renal transplantation Control group, MSC(−) group, MSC(+) group MSCs were injected systemically via the penile vein or via the renal artery Scr↓, BUN↓, renal fibrosis↓, rat survival↑
Wu et al. 2014 [112] BM-MSCs Mouse model of protein overload proteinuria Uninephrectomized (UNX) group, UNX + MSCs group, UNX + BSA group and UNX + BSA + MSCs group Mouse BM-MSCs (1 × 106 cells/mouse) were injected intravenously into uninephrectomized mice CCL-2↓, CCL-5↓, α-SMA↓, Col-IV↓
Zhang et al. 2014 [127] WJ-MSCs-MV IRI rat Sham-operated rats (n  = 6); vehicle-injected IRI rats (n = 6); MVs-injected IRI rats (n = 6) 100 μg MVs in 1 mL vehicle was administered via caudal vein immediately after reperfusion Scr↓, BUN↓, NOX2↓, α-SMA↓, MDA↓, ROS↓, Ki67↓, cell apoptosis↓, renal fibrosis↓
Burgos-Silva et al. 2015 [128] AMSCs Kidney injury mice induced by folic acid FA + AMSCs group, FA group, Bic group, Bic + AMSCs group, control group Via intraperitoneally into FVB mice (1 × 106 cells per animal) CXCL1↓, CCL-5↓, MPO↓, PCNA↓, MCP-1→, IL-2→, IL-6→, GM-CSF→, MIP-1a→, BUN→
Cunha et al. 2015 [129] AF-MSCs IRI rat Group I/R+ vehicle; group I/R + hAFSC; group no injury Cells (1 × 106) were injected into the renal artery Ki67↓, α-SMA↓, CD68↓, Scr→, tubular necrosis↓, tubular hyaline casts↓, renal fibrosis↓
Hattori et al.2015 [130] DMSCs IRI mice SHED group; DMSCs group; control group Administered injected into the subrenal capsule Scr↓, BUN↓, MIP-2↓, IL-1β↓, MCP-1↓, macrophages and neutrophils infiltration↓
Lang et al. 2016 [111] BM-MSCs DN rat (STZ-induced) Normal control group (NC group, n = 10), diabetic nephropathy group (DN group, n = 10), stem cell transplantation group (MSC group, n = 10) 2 × 106 BM-MSCs via tail vein Urinary protein↓, Scr↓, PAI-1↓, TGF-β1↓, Smad3↓, inhibit renal fibrosis
da Silva et al. 2015 [109] BM-MSCs UUO rat Sham, UUO, UUO + BM-MSC, and UUO + CM 1 × 106 BM-MSCs via cava vein Col-lA1↓, α-SMA↓, TNF-α↓, activated caspase 3↓, PCNA ↓(7 days) ↑(14 days); inhibit renal fibrosis
Wang et al. 2016 [115] BM-MSCs UUO mice Sham group, UUO group, UUO + MSCs group, UUO + miR-let7cMSCs group (n = 5/group/time point) Cells (1 × 106) were intraperitoneally administered to each mice Kim-1↓, Col4a1↓, TGF-β1↓, TGF-βR1↓, α-SMA↓, renal fibrosis↓
Zou et al. 2016 [131] uUC-MSC IRI rat Sham group, IRI group, IRI + EVs group and IRI + EVs-RNase group 100 μg MVs in 1 mL vehicle was administered via caudal vein immediately after reperfusion Scr↓, BUN↓, Ki67↑, cell apoptosis↓, HIF-1α↓, VEGF↑, PHD2↑, VHL↑, α-SMA↓, renal fibrosis↓
Eirin et al. 2017 [132] AMSCs RAS pig model Lean group, MetS group, MetS + RAS group, MetS + RAS + EVs group, MetS + RAS + IL10 KD EVs group MSCs were injected via the renal artery Scr↓, macrophages M1↓, macrophages M2↑, M1/M2↓, TNF-α↓ IL-6↓, IL-1β↓, IL-10↑, renal fibrosis↓
Liu et al. 2017 [133] uUC-MSC CM UUO rat Sham group, UUO group, UUO + CM group Injected with hucMSC conditional medium (500 μL) via left renal artery after the surgery GSH↑, ROS↓, MDA↓, α-SMA↓, TGF-β1↓, TNF-α↓, Col-I↓, E-cadherin↑, PCNA↑, cell apoptosis↓, renal interstitial fibrosis↓
Matsui et al. 2017 [116] MSCs UUO rat Sham group, UUO group, sham plus MSCs group, and UUO plus MSCs group (6 animals/group) 1 × 106 BM-MSCs through the renal artery Col-I↓, Col-III↓, fibronectin↓, α-SMA↓, p-STAT3↓, MMP-9↓, TIMP-1↓, TIMP-1/MMP-9↑, inhibit renal fibrosis
Rodrigues et al. 2017 [134] huMSC IRI rat Control group, n = 4; IRI group, n = 9; IRI + huMSC group, n = 5 Cells (1 × 105) were intraperitoneally administered to rat BUN↓, Scr↓, FENa↓, TGF-β1↓, HO-1↓, miR-29a↓, miR-34a↓, miR-29b→, miR-335→, inhibit renal fibrosis
Song et al. 2017 [23] AMSCs UUO rat Sham group, UUO group, UUO + ADSCs group (n = 15) Injected with ADSCs (5 × 106) or vehicle via tail vein MCP-1↓, TLR4↓, TNF-α↓, IL-1β↓, IL-6↓, TGF-β1↓, Smad2/3↓, Smad7↑, α-SMA↓, FSP-1↓, FN↓, E-cadherin↑, renal fibrosis↓, Scr→, BUN→
Zhu et al. 2017 [135] AMSCs IRI mice Normal group, I/R group, I/R + MSCs group Injected with MSCs via tail vein α-SMA↓, PDGFR-β↓, Sox9↑, FN↓, Col-I↓, TGF-β1↓, p-Smad3/Smad3↓, IL-6↓, IL-10↑, IL-1β↓, TNF-α↓, FACS↓, renal fibrosis↓
Rota et al. 2018 [136] uUC-MSC ADR-induced nephropathic athymic rat Control group, ADR group, ADR + BM-MSCs group, ADR + UC-MSCs group, ADR + kPSCs group, ADR + CM-UC-MSCs group Intravenous infusion of MSCs Glomerular podocyte and endothelial cell injury↓
Wu et al. 2018 [137] WJ-MSCs-MV Rat kidney transplant IRI model Sham group (n =  40); kidney transplant IRI group (n =  40); MV-injected kidney transplant IRI group (n =  40) 100 μg MVs in 1 mL vehicle was administered via tail vein after kidney transplantation Scr↓, BUN↓, vWF↓, IL-10↓, TNF-α↓, Ki67↑, cell apoptosis↓, α-SMA↓, TGF-β1↓, HGF↑, renal fibrosis↓
Zou et al. 2018 [138] AMSCs IRI mice Sham group (n = 8), RAS + vehicle group (n = 10), RAS + AMSCs group (n = 10), and RAS + KIM-AMSCs group (n = 10) Cells (5 × 105) were injected through the carotid artery BAX↓, CTGF↓, PAI→, TIMP1→, cell apoptosis↓, inhibit renal fibrosis