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