Search results
The databases mentioned above were searched for this meta-analysis, and we only recruited these studies in mice or rat for evaluation of therapeutic efficiency of MSCs treatment on kidney disease induced by toxicant. Twenty studies [10–36] were eligible and recruited for this meta-analysis, and the flowchart of inclusion of studies is presented in Fig. 1. The included study characteristics are shown in Table 1.
Table 1
Characteristics of the studies included in this meta-analysis.
Author, year | n | Type of animal | Type of injury | MSC type | Number of MSC | Route of delivery | Endpoints for this meta-analysis |
Herrera 2004 | 24 | Mice | Glycerol-induced | BM-MSCs | 1 × 106 | Intravenous injection | Scr |
Bi 2007 | 12 | Mice | Cisplatin-Induced | BM-MSCs | 2 × 105 | Intravenous injection or intraperitoneal injection | Scr, BUN, |
Sun 2008 | 40 | Rat | Glycerol-induced | BM-MSCs | 2 × 106 | Abdominal aorta injection | Scr, BUN, |
Qian 2008 | 6 | Rat | Glycerol-induced | BM-MSCs | 1 × 104 | Intravenous injection | Scr |
Magnasco 2008 | 22 | Rat | Adriamycin-induced | BM-MSCs | 3 × 106 | Intravenous injection | Scr, BUN, UAE, renal damage score |
Bruno 2009 | 16 | Mice | Glycerol-induced | BM-MSCs | - | Intravenous injection | Scr, BUN, MDA, GSH, SOD, renal damage score |
Eliopoulos 2010 | 10 | Mice | Cisplatin-induced | BM-MSCs | 5 × 106 | Intraperitoneal injection | Scr, BUN |
Kim 2012 | 17 | Rat | Cisplatin-induced | AD-MSCs | 5 × 105 | Intravenous injection | Scr, BUN |
Zickri 2012 | 30 | Rat | Adriamycin-induced | hUC-MSCs | 5 × 105 | Intravenous injection | Scr |
Sarhan 2014 | 19 | Rat | Adriamycin-induced | BM-MSCs | 4 × 106 | Intravenous injection | Scr, BUN, UAE, renal pathology, MDA, GSH |
Moustafa 2016 | 80 | Rat | Cisplatin-induced | BM-MSCs | 5 × 106 | Intravenous, intra-arterial or kidney sub capsular injection | Scr, MDA, GSH, SOD |
Elhusseini 2016 | 40 | Rat | Cisplatin-induced | AD-MSCs | 5 × 106 | Intravenous injection | Ccr, renal pathology, MDA, GSH, SOD |
Anan 2016 | 13 | Rat | Adriamycin-induced | BM-MSCs | 1 × 106 | Intravenous injection | Scr, BUN, SOD |
Gad 2017 | 24 | Rat | Methotrexate-induced | BM-MSCs | 2 × 106 | Intraperitoneal injection | Scr, BUN, MDA, GSH |
Rashed 2018 | 20 | Rat | Streptozotocin -induced | BM-MSCs | 1 × 106 | Intravenous injection | Scr, BUN, UAE, Ccr |
Elbaghdady 2018 | 20 | Rat | Cadmium chloride-induced | BM-MSCs | 2 × 106 | Intravenous injection | Scr |
Danjuma 2018 | 16 | Rat | Rifampicin-induced | BM-MSCs | 2.5 × 10⁵ | Intravenous injection | Scr, BUN |
Putra 2019 | 10 | Rat | Gentamicin induced | hUC-MSCs | 1 × 106 | Intraperitoneal injection | Scr, BUN, renal pathology |
Cetinkaya 2019 | 17 | Rat | Aristolochic acid induced | hAMSC | 6 × 10⁵ | Intravenous injection | Scr, BUN |
Selim 2019 | 70 | Rat | Cisplatin-induced | AD-MSCs; BM-MSCs | 4 × 106 | Intravenous injection | Scr, BUN |
Mata-Miranda 2019 | 10 | Mice | Cisplatin-induced | mESCs | 1 × 106 | Intraperitoneal injection | Scr |
Vazquez-Zapien 2019 | 19 | Mice | Cisplatin-induced | mESCs | 1 × 106 | Intraperitoneal injection | Scr |
Minocha 2019 | 3 | Rat | Cisplatin-induced | AFSC | 2 × 106 | Intravenous injection | Scr, BUN |
Sun B 2019 | 10 | Rat | Cisplatin-induced | USCs | 2 × 106 | Intravenous injection | Scr |
Sun 2019 | 6 | Rat | Cisplatin-induced | BM-MSCs | - | Renal parenchyma injection | Scr, BUN |
Zhang 2020 | 9 | Rat | Cisplatin-induced | USCs | 5 × 106 | Subcutaneous injection | Scr, Ccr, renal pathology |
Foroutan 2020 | 6 | Rat | Cisplatin-induced | BM-MSCs | - | Intraperitoneal injection | Scr, BUN |
Quality Assessment Of Included Studies
In the recruited studies, the methodological quality was considered as acceptable, for the result that most of the domains of the recruited investigations were ranked as unclear risk of bias or low risk of bias. Unclear risk of bias mostly detected in performance bias and selection bias. Low risk of bias was mostly occurred in detection bias, reporting bias, and attrition bias. Figure 2 showed the summary of the risk of biases of the recruited investigations.
Scr
26 studies10–15, 17–36 was included to assess the effect of MSCs on Scr, three for 2 days, four for 3-day, five for 4 days, six for 5-day, seven for 6–8 days, ten for 10–15 days, six for 28–30 days, and six for ≥ 42 days, and the results showed that the difference between MSCs treatment group and control group was notable for 2 days, 4 days, 5 days, 6–8 days, 10–15 days, ≥ 42 days (2 days: WMD =-0.88, 95%CI: -1.34, -0.42, P = 0.0002; 4 days: WMD=-0.69, 95%CI: -0.99, -0.39, P < 0.00001; 5 days: WMD=-0.46, 95%CI: -0.67, -0.25, P < 0.0001; 6–8 days: WMD=-0.51, 95%CI: -0.79, -0.22, P = 0.0005; 10–15 days: WMD =-0.38, 95%CI: -0.56, -0.20, P < 0.0001; ≥42 days: WMD =-0.22, 95%CI: -0.39, -0.06, P = 0.007; Fig. 3 and Table 2). However, the difference between MSCs treatment group and control group was not notable for 3 days and 28–30 days (3 days: WMD=-0.09, 95%CI: -0.25, -0.06, P = 0.24; 28–30 days: WMD=-0.59, 95%CI: -1.22, -0.05, P = 0.07; Fig. 3 and Table 2).
Table 2
Meta-analysis of the efficacy of MSC in therapy of renal injury induced by toxicant
Indicators | Time point | Studies | Q test | Model | OR/WMD | P |
| | Number | P-value | selected | (95%CI) | |
Scr | 2 days | 3 | 0.001 | Random | -0.88 (-1.34, -0.42) | 0.0002 |
| 3 days | 4 | 0.0004 | Random | -0.09 (-0.25, 0.06) | 0.24 |
| 4 days | 5 | 0.0002 | Random | -0.69 (-0.99, -0.39) | < 0.00001 |
| 5 days | 6 | < 0.00001 | Random | -0.46 (-0.67, -0.25) | < 0.0001 |
| 6–8 days | 6 | < 0.00001 | Random | -0.51 (-0.79, -0.22) | 0.0005 |
| 10–15 days | 10 | < 0.00001 | Random | -0.38 (-0.56, -0.20) | < 0.0001 |
| 28–30 days | 6 | < 0.00001 | Random | -0.59 (-1.22, 0.05) | 0.07 |
| ≥ 42 days | 6 | < 0.00001 | Random | -0.22 (-0.39, -0.06) | 0.007 |
BUN | 2–3 days | 6 | < 0.00001 | Random | -25.08 (-37.49, -12.67) | < 0.0001 |
| 4–5 days | 7 | < 0.00001 | Random | -24.37 (-31.66, -17.07) | < 0.00001 |
| 6–8 days | 4 | < 0.00001 | Random | -33.44 (-59.37, -7.51) | 0.01 |
| 13–15 days | 4 | < 0.00001 | Random | -13.40 (-32.34, 5.54) | 0.17 |
| ≥ 28 days | 7 | < 0.00001 | Random | -19.85 (-33.35, -6.35) | 0.004 |
UAE | - | 3 | 0.72 | Fixed | -22.66 (-26.41, -18.90) | < 0.00001 |
MDA | - | 4 | 0.41 | Fixed | -17.21 (-20.38, -14.04) | < 0.00001 |
GSH | - | 4 | < 0.00001 | Random | 4.62 (2.74, 6.50) | < 0.00001 |
SOD | - | 3 | < 0.00001 | Random | 5.42 (2.92, 7.93) | < 0.0001 |
Renal pathology | | | | | | |
Inflammatory cells | - | 4 | < 0.00001 | Random | -2.66 (-3.83, -1.49) | < 0.00001 |
Necrotic tubule | - | 2 | < 0.00001 | Random | -2.58 (-4.75, -0.40) | 0.02 |
Regenerative tubules | - | 2 | - | Fixed | 6.00 (3.45, 8.55) | < 0.00001 |
Renal interstitial fibrosis | - | 3 | < 0.00001 | Random | -5.82 (-7.41, -4.23) | < 0.00001 |
Note: Scr: serum creatinine; BUN: blood urea nitrogen; UAE: urinary albumin excretion; Ccr: creatinine clearance rate; MDA: malondialdehyde; GSH: L-Glutathione; SOD: superoxide dismutase. |
BUN
17 studies10–14, 17, 18, 20, 21, 23, 25–28, 31–33, 35, 36 was included to assess the effect of MSCs on BUN, six for 2–3 days, seven for 4–5 days, four for 6–8 days, four for 13–15 days, and seven for ≥ 28 days, and the results indicated that the difference between MSCs treatment group and control group was notable for 2–3 days, 4–5 days, 6–8 days, ≥ 28 days (2–3 days: WMD =-25.08, 95%CI: -37.49, -12.67, P < 0.0001; 4–5 days: WMD=-24.37, 95%CI: -31.66, -17.07, P < 0.00001; 6–8 days: WMD=-33.44, 95%CI: -59.37, -7.51, P = 0.01; ≥28 days: WMD=-19.85, 95%CI: -33.35, -6.35, P = 0.004; Fig. 4 and Table 2). However, the difference between MSCs treatment group and control group was not notable for 13–15 days (WMD=-13.40, 95%CI: -32.34, 5.54, P = 0.17; Fig. 4 and Table 2).
Urinary Albumin Excretion
Three studies21, 25, 26 were recruited into the meta-analysis for the assessment of MSCs on UAE. The results showed that the MSCs group had lower UAE than the control group (WMD=-22.66, 95%CI: -26.41, -18.90, P < 0.00001; Table 2).
Oxidative Stress
In this meta-analysis, four studies16, 18, 22, 26 were included for the assessment of MDA, four16, 18, 22, 26 for GSH, three10, 16, 22 for SOD. The results indicated that the difference between MSCs treatment group and control group was notable for MDA, GSH, SOD (MDA: WMD=-17.21, 95%CI: -20.38, -14.04, P < 0.00001; GSH: WMD = 4.62, 95%CI: 2.74, 6.50, P < 0.00001; SOD: WMD = 5.42, 95%CI: 2.92, 7.93, P < 0.0001; Table 2).
Assessment Of Renal Pathology
Four studies16, 23, 26, 34 for inflammatory cells, two studies16, 26 for necrotic tubule, two studies16, 26 for regenerative tubules and three studies16, 26, 34 for renal interstitial fibrosis were included into this meta-analysis. The results indicated that the difference of inflammatory cells, necrotic tubule, regenerative tubules, renal interstitial fibrosis between MSCs treatment and control group was significant (inflammatory cells: WMD=-2.66, 95%CI: -3.83, -1.49, P < 0.00001; necrotic tubule: WMD=-2.58, 95%CI: -4.75, -0.40, P = 0.02; regenerative tubules: WMD = 6.00, 95%CI: 3.45, 8.55, P < 0.00001; renal interstitial fibrosis: WMD=-5.82, 95%CI: -7.41, -4.23, P < 0.00001; Table 2).
Publication bias
The publication bias was tested in this meta-analysis, and a funnel plot generated used STATA 12.0 for the primary outcome, and Begg’stest and Egger’s test suggested that publication bias was found (Egger’s: P = 0.000, Begg’s: P = 0.000; Fig. 5).