Stem Cells International

Stem Cells International / 2020 / Article
Special Issue

Stem Cell Applications in Regenerative Medicine for Kidney Diseases

View this Special Issue

Research Article | Open Access

Volume 2020 |Article ID 1873921 | https://doi.org/10.1155/2020/1873921

Tianbiao Zhou, Chunling Liao, Shujun Lin, Wenshan Lin, Hongzhen Zhong, Shuangyi Huang, "The Efficacy of Mesenchymal Stem Cells in Therapy of Acute Kidney Injury Induced by Ischemia-Reperfusion in Animal Models", Stem Cells International, vol. 2020, Article ID 1873921, 11 pages, 2020. https://doi.org/10.1155/2020/1873921

The Efficacy of Mesenchymal Stem Cells in Therapy of Acute Kidney Injury Induced by Ischemia-Reperfusion in Animal Models

Academic Editor: Erika B. Rangel
Received17 Mar 2020
Revised03 Jul 2020
Accepted18 Jul 2020
Published03 Aug 2020

Abstract

Mesenchymal stem cells (MSCs), discovered and isolated from the bone marrow in the 1960s and with self-renewal capacity and multilineage differentiation potential, have valuable immunomodulatory abilities. Acute kidney injury (AKI) refers to rapid renal failure, which exhibits as quickly progressive decreasing excretion in few hours or days. This study was performed to assess the efficacy of MSCs in the treatment of AKI induced by ischemia-reperfusion using a meta-analysis method. A literature search using corresponding terms was performed in the following databases: Embase, Cochrane Library, PubMed, and ISI Web of Science databases up to Dec 31, 2019. Data for outcomes were identified, and the efficacy of MSCs for AKI was assessed using Cochrane Review Manager Version 5.3. Nineteen studies were eligible and recruited for this meta-analysis. MSC treatment can reduce the Scr levels at 1 day, 2 days, 3 days, 5 days, and >7 days (1 day: , 95% CI: -0.78, -0.34, ; 2 days: , 95% CI: -0.89, -0.28, ; 3 days: , 95% CI: -0.84, -0.45, ; 5 days: , 95% CI: -0.54, -0.16, ; and >7 days: , 95% CI: -0.36, -0.08, ) and can reduce the levels of BUN at 1 day, 2 days, 3 days, and 5 days (1 day: , 95% CI: -18.80, -4.64, ; 2 days: , 95% CI: -40.15, -27.05, ; 3 days: , 95% CI: -26.15, -16.14, ; and 5 days: , 95% CI: -11.06, -6.69, ), and it also can reduce the levels of proteinuria at 3 days and >7 days and alleviate the renal damage in animal models of AKI. In conclusion, MSCs might be a promising therapeutic agent for AKI induced by ischemia-reperfusion.

1. Introduction

Mesenchymal stem cells (MSCs), discovered and isolated from bone marrow in the 1960s and with self-renewal capacity and multilineage differentiation potential, have valuable immunomodulatory abilities and exist in almost all human tissue lineages [13]. MSCs can secrete a wide range of growth factors, such as cytokines, chemokines, and extracellular vesicles—collectively termed the secretome [4, 5]. MSCs support revascularization, inhibition of inflammation, regulation of apoptosis, and promotion of the release of beneficial factors [6, 7]. MSC transplantation is a fast-developing therapy in cell-based therapies and regenerative medicine [810]. Thus, they are regarded as a promising candidate for the repair and regeneration of some diseases [6, 1113].

Acute kidney injury (AKI) refers to rapid renal failure, which exhibits as quickly progressive decreasing excretion in few hours or days [14]. It is mainly characterized by oliguria or accumulation of serum creatinine, which is elevated by 0.3 mg/dl within 48 hours or more than 50% of the baseline [15, 16]. Ischemia-reperfusion is one of the common pathological conditions in AKI. It indicates that organs regain perfusion after temporary restriction of blood flow. In response to the sudden interruption of blood supply in IRI, oxidative stress and inflammation appear frequently in AKI [17, 18]. A series of cytokines, such as interleukins and tumor necrosis factor-α (TNF-α), are activated in this procedure. By promoting oxidative stress or apoptotic processes, they finally enhance renal inflammation and dysfunction [1820].

This study was performed to assess the efficacy of MSCs in the treatment of AKI induced by ischemia-reperfusion using a meta-analysis method.

2. Materials and Methods

2.1. Search Strategy

A comprehensive search strategy for literature, which was restricted to English-language literature, was conducted in the Embase, Cochrane Library, PubMed, and ISI Web of Science databases up to Dec 31, 2019, using the following search corresponding terms: (mesenchymal stem cells OR MSC OR MSCs OR multipotent stromal cells OR mesenchymal stromal cells OR mesenchymal progenitor cells OR stem cells OR stromal cells) AND (acute kidney injury OR AKI OR acute renal failure OR ARF OR renal ischemia-reperfusion). The manual reference searches in the recruited articles were also conducted to identify additionally eligible reports.

2.2. Inclusion and Exclusion Criteria
2.2.1. Inclusion Criteria

The inclusion criteria are the following: (1) research object: animal experiment used mice or rat, (2) object of the study: AKI, (3) interventions for study: MSCs for treatment, and (4) outcome: efficacy.

2.2.2. Exclusion Criteria

The exclusion criteria are the following: (1) letters, case reports, reviews, clinical studies, editorials, meta-analysis, and systematic reviews; (2) studies lacking the targeted indicators or number of the case group or the control group and conducted in humans; (3) the AKI disease not induced by ischemia-reperfusion; and (4) the therapeutic regimen for AKI including other agents with undefined effects.

2.3. Outcome Measures

The following outcomes regarding the efficacy of MSC treatment on AKI induced by ischemia-reperfusion were identified from the recruited studies: serum creatinine (Scr), blood urea nitrogen (BUN), proteinuria, malondialdehyde (MDA), L-glutathione (GSH), CAT, superoxide dismutase (SOD), NADPH oxidase-1 (NOX1), NADPH oxidase-2 (NOX2), poly(ADP-ribose) polymerase-1 (PARP1), Caspase 3 (mRNA and protein), tumor necrosis factor-α (TNF-α), Bcl-2 associated X protein (Bax), nuclear factor kappa beta (NFκB), interleukin 1β (IL1β; mRNA and protein), interleukin 4 (IL4), interleukin 6 (IL6) mRNA, interleukin 10 (IL10; mRNA and protein), transforming growth factor-β1 (TGF-β), and renal damage score. When disagreements were addressed, a mutual consensus was conducted to resolve it.

2.4. Quality Assessment

The Cochrane Handbook for Interventions was used to evaluate the methodological quality by two investigators independently (Tianbiao Zhou and Chunling Liao). The principal assessment included the following sections for each investigation: selection bias, attrition bias, performance bias, detection bias, reporting bias, and other bias. Each item was classified as unclear, high risk, or low risk.

2.5. Statistical Analysis

Review Manager Version 5.3 was used to explore whether MSC treatment can get a good efficacy on AKI induced by ischemia-reperfusion, and STATA 12.0 was applied to test the publication bias. Heterogeneity of variation among individual studies was quantified and described with . When the value was ≥0.1, the fixed-effects model was used, based on the heterogeneity test. Otherwise, we will use the random-effects model to pool the results for the meta-analysis. Weighted mean differences (WMDs) for the mean values were used to compute the continuous variables, and 95% confidence intervals (95% CI) were calculated for the included studies using the Mantel-Haenszel (M-H) method. Both Begg’s rank correlation test and Egger’s linear regression method were applied to detect the publication bias among the studies. A value < 0.05 was considered as statistical significance.

3. Results

3.1. 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 MSC treatment on AKI. Nineteen studies [2139] were eligible and recruited for this meta-analysis, and the flowchart of inclusion of studies is presented in Figure 1. The included study characteristics are shown in Table 1.


Author, yearType of animalMSC typeNumber of MSCRoute of deliveryEndpoints for this meta-analysis

Tögel, 200512RatBM-MSCsArteryScr
Duffield, 200514MiceBM-MSCsIntravenousScr
Tögel, 200936RatBM-MSCsArteryScr
Burst, 201028RatBM-MSCsIntravenousScr
La Manna, 201112RatFM-MSCsIntravenousScr, renal damage score
Zhuo, 201324RatBM-MSCsIntravenous or arteryScr, BUN, MDA, GSH, SOD, renal damage score
Sadek, 201310RatBM-MSCsIntravenousScr, BUN
Zhao, 201420RatBM-MSCsIntravenousScr, BUN, IL6 mRNA
Tsuda, 201454RatFM-MSCsIntravenousScr, BUN, renal damage score
Hattori, 201522MiceBM-MSCsKidney subcapsular injectionScr, BUN
Lin, 201616RatAD-MSCsIntravenousScr, BUN, proteinuria, NOX1, NOX2, PARP1, Caspase 3 protein, Bax, TNF-α, NFκB, IL1β protein, TGF-β, renal damage score
Hussein, 201636RatAD-MSCsIntravenousScr, BUN, Caspase 3 mRNA
Sheashaa, 201642RatAD-MSCsIntravenousScr, MDA
Zhang, 201712RatAD-MSCsIntravenousScr, proteinuria, TNF-α, IL1β mRNA, IL6 mRNA, IL10 mRNA, TGF-β
Fahmy, 201716RatUC-MSCsIntravenousScr, BUN, proteinuria, MDA, GSH, CAT
Sung, 201716RatAD-MSCsIntravenousScr, BUN, proteinuria, NOX1, NOX2, PARP1, Caspase 3 protein, Bax, TNF-α, NFκB, IL1β protein, IL4, IL10 protein, renal damage score
Guo, 201836MiceUC-MSCsIntravenousScr, BUN, TNF-α, IL1β protein, IL10 protein
Ko, 201812RatiPSC-MSCIntravenousScr, BUN, proteinuria, NOX1, NOX2, PARP1, Caspase 3 protein, Bax, TNF-α, NFκB, IL4, IL10 protein
Alzahrani, 201920RatBM-MSCsArteryScr, BUN, MDA, CAT, SOD, NOX2, PARP1, Caspase 3 mRNA, IL1β mRNA, IL10 mRNA, renal damage score

Note: FM-MSCs: fetal membrane-derived mesenchymal stem cells; BM-MSC: bone marrow-derived mesenchymal stem cells; AD-MSCs: adipose tissue-derived MSCs; UC-MSCs: umbilical cord mesenchymal stem cells; iPSC-MSCs: inducible pluripotent stem cell-derived mesenchymal stem cells; Scr: serum creatinine; BUN: blood urea nitrogen; MDA: malondialdehyde; GSH: L-glutathione; SOD: superoxide dismutase; NOX1: NADPH oxidase-1; NOX2: NADPH oxidase-2; PARP1: poly(ADP-ribose) polymerase-1; TNF-α: tumor necrosis factor-α; Bax: Bcl-2 associated X protein; NFκB: nuclear factor kappa beta; IL1β: interleukin 1β; IL4: interleukin 4; IL6: interleukin 6; IL10: interleukin 10; TGF-β: transforming growth factor-β.
3.2. 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 was mostly detected in performance bias and selection bias. Low risk of bias mostly occurred in detection bias, reporting bias, and attrition bias. Figure 2 shows the summary of the risk of biases of the recruited investigations.

3.3. Scr

19 studies [2139] were included to assess the effect of MSCs on Scr, 12 for 1 day, four for 2 days, 14 for 3 days, four for 5 days, seven for 7 days, and five for >7 days, and the results showed that the difference between the MSC treatment group and the control group was notable for 1 day, 2 days, 3 days, 5 days, and >7 days (1 day: , 95% CI: -0.78, -0.34, ; 2 days: , 95% CI: -0.89, -0.28, ; 3 days: , 95% CI: -0.84, -0.45, ; 5 days: , 95% CI: -0.54, -0.16, ; and >7 days: , 95% CI: -0.36, -0.08, ; Figure 3 and Table 2). However, the difference between the MSC treatment group and the control group was not notable for 7 days (, 95% CI: -0.28, -0.00, ; Figure 3 and Table 2).


IndicatorsTimepointStudy number test valueModel selectedWMD (95% CI)

Scr1 day13<0.00001Random-0.56 (-0.78, -0.34)<0.00001
2 days50.0002Random-0.58 (-0.89, -0.28)0.0002
3 days15<0.00001Random-0.65 (-0.84, -0.45)<0.00001
5 days4<0.00001Random-0.35 (-0.54, -0.16)0.0003
7 days7<0.00001Random-0.14 (-0.28, -0.00)0.05
>7 days5<0.00001Random-0.22 (-0.36, -0.08)0.002
BUN1 day70.04Random-11.72 (-18.80, -4.64)0.001
2 days30.38Fixed-33.60 (-40.15, -27.05)<0.00001
3 days10<0.00001Random-21.14 (-26.15, -16.14)<0.00001
5 days20.20Fixed-8.88 (-11.06, -6.69)<0.00001
7 days20.79Fixed-0.72 (-13.49, -12.05)0.91
>7 days2<0.00001Random-90.84 (-257.31, 75.62)0.28
Proteinuria3 days3<0.00001Random-0.45 (-0.61, -0.30)<0.00001
>7 days20.21Fixed-108.55 (-110.31, -106.78)<0.00001
MDA40.0001Random-5.51 (-10.57, -0.45)0.03
GSH20.0002Random-31.40 (-21.52, 84.31)0.24
CAT2<0.00001Random10.82 (-4.30, 25.95)0.16
SOD20.41Fixed18.95 (16.86, 21.04)<0.00001
NOX13<0.00001Random-0.32 (-0.54, -0.10)0.004
NOX24<0.00001Random-0.19 (-0.28, -0.10)<0.0001
PARP14<0.00001Random-0.22 (-0.34, -0.09)0.0006
Caspase 3 (mRNA)2<0.00001Random-3.40 (-6.13, -0.68)0.01
Caspase 3 (protein)3<0.00001Random-0.15 (-0.21, -0.08)<0.00001
Bax3<0.00001Random-0.25 (-4.42, -0.08)0.004
TNF-α5<0.00001Random-0.15 (-0.31, -0.02)0.08
NFκB3<0.00001Random-0.36 (-0.66, -0.05)0.02
IL1β (mRNA)20.007Random-3.26 (-4.37, -2.15)<0.00001
IL1β (protein)3<0.00001Random-0.37 (-0.57, -0.17)0.0003
IL42<0.00001Random0.13 (0.02, 0.23)0.02
IL6 (mRNA)2<0.00001Random-2.34 (-4.75, 0.07)0.06
IL10 (mRNA)20.13Fixed0.27 (0.24, 0.29)<0.00001
IL10 (protein)3<0.00001Random0.45 (0.04, 0.86)0.03
TGF-β2<0.00001Random-18.89 (-55.79, 18.02)0.32
Renal damage score1 day4<0.00001Random-14.50 (-19.10, -9.90)<0.00001
3 days4<0.00001Random-1.19 (-1.72, -0.66)<0.0001

Note: Scr: serum creatinine; BUN: blood urea nitrogen; MDA: malondialdehyde; GSH: L-glutathione; SOD: superoxide dismutase; NOX1: NADPH oxidase-1; NOX2: NADPH oxidase-2; PARP1: poly(ADP-ribose) polymerase-1; TNF-α: tumor necrosis factor-α; Bax: Bcl-2 associated X protein; NFκB: nuclear factor kappa beta; IL1β: interleukin 1β; IL4: interleukin 4; IL6: interleukin 6; IL10: interleukin 10; TGF-β: transforming growth factor-β.
3.4. BUN

12 studies [21, 2428, 30, 31, 33, 36, 38, 39] were included to assess the effect of MSCs on Scr, 7 for 1 day, 3 for 2 days, 10 for 3 days, 2 for 5 days, 2 for 7 days, and 2 for >7 days, and the results indicated that the difference between the MSC treatment group and the control group was notable for 1 day, 2 days, 3 days, and 5 days (1 day: , 95% CI: -18.80, -4.64, ; 2 days: , 95% CI: -40.15, -27.05, ; 3 days: , 95% CI: -26.15, -16.14, ; and 5 days: , 95% CI: -11.06, -6.69, ; Figure 4 and Table 2). However, the difference between the MSC treatment group and the control group was not notable for 7 days and >7 days (7 days: , 95% CI: -13.49, -12.05, ; >7 days: , 95% CI: -257.31, 75.62, ; Figure 4 and Table 2).

3.5. Proteinuria

Five studies [24, 28, 30, 33, 37] were recruited into the meta-analysis for the assessment of MSCs on proteinuria, three for 3 days and two for >7 days. The results showed that the MSC group had lower proteinuria than the control group for 3 days and for >7 days (3 days: , 95% CI: -0.61, -0.30, ; >7 days: , 95% CI: -110.31, -106.78, ; Table 2).

3.6. Oxidative Stress and Apoptosis-Related Factors

In this meta-analysis, four studies [21, 24, 32, 39] were included for the assessment of MDA, two [24, 39] for GSH, two [21, 24] for CAT, two [21, 39] for SOD, three [28, 30, 33] for NOX1, four [21, 28, 30, 33] for NOX2, four [21, 28, 30, 33] for PARP1, two [21, 27] for Caspase 3 (mRNA), three [28, 30, 33] for Caspase 3 (protein), and three [28, 30, 33] for Bax. The results indicated that the difference between the MSC treatment group and the control group was notable for MDA, SOD, NOX1, NOX2, PARP1, Caspase 3 mRNA, Caspase 3 protein, and Bax (MDA: , 95% CI: -10.57, -0.45, ; SOD: , 95% CI: 16.86, 21.04, ; NOX1: , 95% CI: -0.54, -0.10, ; NOX2: , 95% CI: -0.28, -0.10, ; PARP1: , 95% CI: -0.34, -0.09, ; Caspase 3 mRNA: , 95% CI: -6.13, -0.68, ; Caspase 3 protein: , 95% CI: -0.21, -0.08, ; and Bax: , 95% CI: -4.42, -0.08, ; Table 2). However, the difference for GSH and CAT between the MSC treatment and the control group was not significant (GSH: , 95% CI: -21.52, 84.31, ; CAT: , 95% CI: -4.30, 25.95, ; Table 2).

3.7. Assessment of Cytokines

The levels of TNF-α, NFκB, IL1β (mRNA), IL1β (protein), IL4, IL6 (mRNA), IL10 (mRNA), IL10 (protein), and TGF-β were detected, and five studies [25, 28, 30, 33, 37] for TNF-α, three studies [28, 30, 33] for NFκB, two studies [21, 37] for IL1β (mRNA), three studies [25, 30, 33] for IL1β (protein), two studies [28, 33] for IL4, two studies [37, 38] for IL6 (mRNA), two studies [21, 37] for IL10 (mRNA), three studies [25, 28, 33] for IL10 (protein), and two studies [30, 37] for TGF-β were recruited for the evaluation of the treatment effect of MSC treatment on these cytokines. We also found that the difference between the MSC treatment group and the control group was significant for NFκB, IL1β mRNA and protein, IL4, and IL10 mRNA and protein (NFκB: , 95% CI: -0.66, -0.05, ; IL1β mRNA: , 95% CI: -4.37, -2.15, ; IL1β protein: , 95% CI: -0.57, -0.17, ; IL4: , 95% CI: 0.02, 0.23, ; IL10 mRNA: , 95% CI: 0.24, 0.29, ; and IL10 protein: , 95% CI: 0.04, 0.86, ; Table 2). However, the difference for TNF-α, IL6 mRNA, and TGF-β between the MSC treatment and control groups was not significant (TNF-α: , 95% CI: -0.31, -0.02, ; IL6 mRNA: , 95% CI: -4.75, 0.07, ; and TGF-β: , 95% CI: -55.79, 18.02, ; Table 2).

3.8. Assessment of Renal Damage Score

Four studies [29, 35, 36, 39] for 1 day and four studies [21, 30, 33, 36] for 3 days were included in this meta-analysis. The results indicated that the difference of the renal damage score for 1 day and for 3 days between the MSC treatment and control groups was significant (1 day: , 95% CI: -19.10, -9.90, ; 3 days: , 95% CI: -1.72, -0.66, ; Table 2).

3.9. Publication Bias

The publication bias was tested in this meta-analysis, and a funnel plot was generated used STATA 12.0 for the primary outcome, and Begg’s test and Egger’s test suggested that publication bias was found (Egger’s: , Begg’s: ; Figure 5).

4. Discussion

In this study, we found that MSC treatment can reduce the Scr levels at 1 day, 2 days, 3 days, 5 days, and >7 days in animal models of AKI. Furthermore, MSC treatment also can reduce the levels of BUN at 1 day, 2 days, 3 days, and 5 days, and it also can reduce the levels of proteinuria at 3 days and >7 days. The renal damage score was also detected, and we found that MSC treatment can significantly reduce the renal damage score in animal models of AKI. The results indicated that MSCs can get a protective role against AKI.

The dysfunction of oxidative stress is associated with AKI induced by ischemia-reperfusion, and cell injury or cell apoptosis takes part in the pathogenesis of AKI. As those mentioned above, the result indicated that the MSCs can improve the injury of AKI in animal models. We further collected the data about oxidative stress and apoptosis-related factors. In this study, the results indicated that MSC treatment can reduce MDA, NOX1, NOX2, PARP1, Caspase 3, and Bax and increase SOD. Previously, there were some studies indicating that MSC treatment can suppress oxidative stress and take the protective role. Song et al. [40] conducted a study in adriamycin-induced nephropathy rats and reported that MSCs can attenuate the nephropathy by diminishing oxidative stress and inhibiting the inflammation via downregulation of NFκB. de Godoy et al. [41] evaluate the neuroprotective potential of MSCs against the deleterious impact of amyloid-β peptide on hippocampal neurons and reported that MSCs protect hippocampal neurons against oxidative stress and synapse damage. Chang et al. [42] reported that MSC transplantation successfully alleviates glomerulonephritis through antioxidation and antiapoptosis in nephritic rats.

Activation of some cytokines takes part in the pathogenesis of AKI induced by ischemia-reperfusion. In our study, we found that MSC treatment can inhibit NFκB and IL1β and increased IL4 and IL10. Song et al. [40] indicated that MSCs can attenuate the nephropathy by inhibiting oxidative stress and alleviating the inflammation via inhibiting NFκB. There were also some studies reporting the association of MSCs with ILs.

However, there were some limitations in our meta-analysis. First, the sample size for the recruited investigation was small, and the longer-term endpoints were missed. Furthermore, the animal type was different (mouse and rat), and the normal values of the parameters, such as BUN and Scr, for rats or mice were different. The type of MSCs and the dose of MSCs administered were not exactly the same. These factors mentioned above may cause our results to be less robust.

5. Conclusions

MSC treatment can reduce the Scr levels at 1 day, 2 days, 3 days, 5 days, and >7 days and can reduce the levels of BUN at 1 day, 2 days, 3 days, and 5 days, and it also can reduce the levels of proteinuria at 3 days and >7 days and alleviate the renal damage in animal models of AKI. The results indicated that MSCs can get a protective role against AKI. However, more well-designed studies with larger sample sizes and longer-term endpoints should be conducted to identify additional and robust outcomes in the future.

Data Availability

The data supporting this meta-analysis are from previously reported studies and datasets, which have been cited. The processed data are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no competing interests.

Authors’ Contributions

TBZ contributed to the conception and design of the study. TBZ and CLL were responsible for collection of data and performing the statistical analysis and manuscript preparation. SJL, WSL, HZZ, and SYH were responsible for checking the data. All authors were responsible for drafting the manuscript, read, and approved the final version.

Acknowledgments

This study was supported by the Shantou Science and Technology Project (Shanfuke [2019] 106: 190606165268433).

References

  1. S. N. Li and J. F. Wu, “TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment,” Stem Cell Research & Therapy, vol. 11, no. 1, p. 41, 2020. View at: Publisher Site | Google Scholar
  2. A. Wang, J. Liu, X. Zhuang et al., “Identification and comparison of piRNA expression profiles of exosomes derived from human stem cells from the apical papilla and bone marrow mesenchymal stem cells,” Stem Cells and Development, vol. 29, no. 8, pp. 511–520, 2020. View at: Publisher Site | Google Scholar
  3. D. K. W. Ocansey, B. Pei, Y. Yan et al., “Improved therapeutics of modified mesenchymal stem cells: an update,” Journal of Translational Medicine, vol. 18, no. 1, p. 42, 2020. View at: Publisher Site | Google Scholar
  4. C. J. Cunningham, R. Wong, J. Barrington, S. Tamburrano, E. Pinteaux, and S. M. Allan, “Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke,” Stem Cell Research & Therapy, vol. 11, no. 1, p. 32, 2020. View at: Publisher Site | Google Scholar
  5. F. C. C. van Rhijn-Brouwer, B. W. M. van Balkom, D. A. Papazova et al., “Paracrine proangiogenic function of human bone marrow-derived mesenchymal stem cells is not affected by chronic kidney disease,” Stem Cells International, vol. 2019, Article ID 1232810, 12 pages, 2019. View at: Publisher Site | Google Scholar
  6. Y. Yang, M. Pang, Y. Y. Chen et al., “Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial,” Neural Regeneration Research, vol. 15, no. 8, pp. 1532–1538, 2020. View at: Publisher Site | Google Scholar
  7. J. Wang, R. Hu, Q. Xing et al., “Exosomes derived from umbilical cord mesenchymal stem cells alleviate mifepristone-induced human endometrial stromal cell injury,” Stem Cells International, vol. 2020, Article ID 6091269, 9 pages, 2020. View at: Publisher Site | Google Scholar
  8. L. C. F. Coppin, F. Smets, J. Ambroise, E. E. M. Sokal, and X. Stéphenne, “Infusion-related thrombogenesis by liver-derived mesenchymal stem cells controlled by anticoagulant drugs in 11 patients with liver-based metabolic disorders,” Stem Cell Research & Therapy, vol. 11, no. 1, p. 51, 2020. View at: Publisher Site | Google Scholar
  9. J. Huang, J. Huang, X. Ning et al., “CT/NIRF dual-modal imaging tracking and therapeutic efficacy of transplanted mesenchymal stem cells labeled with Au nanoparticles in silica-induced pulmonary fibrosis,” Journal of Materials Chemistry B, vol. 8, no. 8, pp. 1713–1727, 2020. View at: Publisher Site | Google Scholar
  10. X. Wang, T. Liang, J. Qiu et al., “Melatonin reverses the loss of stemness induced by TNF-α in human bone marrow mesenchymal stem cells through upregulation of YAP expression,” Stem Cells International, vol. 2019, Article ID 6568394, 16 pages, 2019. View at: Publisher Site | Google Scholar
  11. D. Parate, N. D. Kadir, C. Celik et al., “Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration,” Stem Cell Research & Therapy, vol. 11, no. 1, p. 46, 2020. View at: Publisher Site | Google Scholar
  12. E. M. Ghaffary and S. M. A. Froushani, “Immunomodulatory benefits of mesenchymal stem cells treated with caffeine in adjuvant-induced arthritis,” Life Sciences, vol. 246, article 117420, 2020. View at: Publisher Site | Google Scholar
  13. W. Sun, Q. Zhu, L. Yan, and F. Shao, “Mesenchymal stem cells alleviate acute kidney injury via miR-107-mediated regulation of ribosomal protein S19,” Annals of Translational Medicine, vol. 7, no. 23, p. 765, 2019. View at: Publisher Site | Google Scholar
  14. R. Bellomo, J. A. Kellum, and C. Ronco, “Acute kidney injury,” Lancet, vol. 380, no. 9843, pp. 756–766, 2012. View at: Publisher Site | Google Scholar
  15. A. S. Levey and M. T. James, “Acute kidney injury,” Annals of Internal Medicine, vol. 167, no. 9, pp. ITC66–ITC80, 2017. View at: Publisher Site | Google Scholar
  16. J. Yoo, J. S. Lee, J. Lee et al., “Relationship between duration of hospital-acquired acute kidney injury and mortality: a prospective observational study,” The Korean Journal of Internal Medicine, vol. 30, no. 2, pp. 205–211, 2015. View at: Publisher Site | Google Scholar
  17. E. E. Hesketh, A. Czopek, M. Clay et al., “Renal ischaemia reperfusion injury: a mouse model of injury and regeneration,” Journal of Visualized Experiments, vol. 88, p. e51816, 2014. View at: Publisher Site | Google Scholar
  18. M. Malek and M. Nematbakhsh, “Renal ischemia/reperfusion injury; from pathophysiology to treatment,” Journal of Renal Injury Prevention, vol. 4, no. 2, pp. 20–27, 2015. View at: Publisher Site | Google Scholar
  19. N. S. A. Patel, P. K. Chatterjee, R. Di Paola et al., “Endogenous interleukin-6 enhances the renal injury, dysfunction, and inflammation caused by ischemia/reperfusion,” The Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 3, pp. 1170–1178, 2005. View at: Publisher Site | Google Scholar
  20. S. Banaei and L. Rezagholizadeh, “The role of hormones in renal disease and ischemia-reperfusion injury,” Iranian Journal of Basic Medical Sciences, vol. 22, no. 5, pp. 469–476, 2019. View at: Publisher Site | Google Scholar
  21. F. A. Alzahrani, “Melatonin improves therapeutic potential of mesenchymal stem cells-derived exosomes against renal ischemia-reperfusion injury in rats,” American Journal of Translational Research, vol. 11, no. 5, pp. 2887–2907, 2019. View at: Google Scholar
  22. V. R. Burst, M. Gillis, F. Pütsch et al., “Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury,” Nephron. Experimental Nephrology, vol. 114, no. 3, pp. e107–e116, 2010. View at: Publisher Site | Google Scholar
  23. J. S. Duffield, K. M. Park, L. L. Hsiao et al., “Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells,” The Journal of Clinical Investigation, vol. 115, no. 7, pp. 1743–1755, 2005. View at: Publisher Site | Google Scholar
  24. S. R. Fahmy, A. M. Soliman, M. El Ansary, S. A. Elhamid, and H. Mohsen, “Therapeutic efficacy of human umbilical cord mesenchymal stem cells transplantation against renal ischemia/reperfusion injury in rats,” Tissue & Cell, vol. 49, no. 3, pp. 369–375, 2017. View at: Publisher Site | Google Scholar
  25. Q. Guo and J. Wang, “Effect of combination of vitamin E and umbilical cord-derived mesenchymal stem cells on inflammation in mice with acute kidney injury,” Immunopharmacology and Immunotoxicology, vol. 40, no. 2, pp. 168–172, 2018. View at: Publisher Site | Google Scholar
  26. Y. Hattori, H. Kim, N. Tsuboi et al., “Therapeutic potential of stem cells from human exfoliated deciduous teeth in models of acute kidney injury,” PLoS One, vol. 10, no. 10, p. e0140121, 2015. View at: Publisher Site | Google Scholar
  27. A. M. Hussein, N. Barakat, A. Awadalla et al., “Modulation of renal ischemia/reperfusion in rats by a combination of ischemic preconditioning and adipose-derived mesenchymal stem cells (ADMSCs),” Canadian Journal of Physiology and Pharmacology, vol. 94, no. 9, pp. 936–946, 2016. View at: Publisher Site | Google Scholar
  28. S.-F. Ko, Y.-T. Chen, C. G. Wallace et al., “Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury,” American Journal of Translational Research, vol. 10, no. 10, pp. 3053–3067, 2018. View at: Google Scholar
  29. G. La Manna, F. Bianchi, M. Cappuccilli et al., “Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model,” Cell Transplantation, vol. 20, no. 8, pp. 1193–1208, 2011. View at: Publisher Site | Google Scholar
  30. K. C. Lin, H. K. Yip, P. L. Shao et al., “Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury,” International Journal of Cardiology, vol. 216, pp. 173–185, 2016. View at: Publisher Site | Google Scholar
  31. E. M. Sadek, N. M. Afifi, L. I. A. Elfattah, and M. A. A.-E. Mohsen, “Histological Study on Effect of Mesenchymal Stem Cell Therapy on Experimental Renal Injury Induced by Ischemia/Reperfusion in Male Albino Rat,” International Journal of Stem Cells, vol. 6, no. 1, pp. 55–66, 2013. View at: Publisher Site | Google Scholar
  32. H. U. S. S. E. I. N. SHEASHAA, A. H. M. E. D. LOTFY, F. A. T. M. A. ELHUSSEINI et al., “Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats,” Experimental and Therapeutic Medicine, vol. 11, no. 5, pp. 1573–1580, 2016. View at: Publisher Site | Google Scholar
  33. P. H. Sung, H. J. Chiang, C. G. Wallace et al., “Exendin-4-assisted adipose derived mesenchymal stem cell therapy protects renal function against co-existing acute kidney ischemia-reperfusion injury and severe sepsis syndrome in rat,” American Journal of Translational Research, vol. 9, no. 7, pp. 3167–3183, 2017. View at: Google Scholar
  34. F. Tögel, A. Cohen, P. Zhang, Y. Yang, Z. Hu, and C. Westenfelder, “Autologous and Allogeneic Marrow Stromal Cells Are Safe and Effective for the Treatment of Acute Kidney Injury,” Stem Cells and Development, vol. 18, no. 3, pp. 475–486, 2009. View at: Publisher Site | Google Scholar
  35. F. Tögel, Z. Hu, K. Weiss, J. Isaac, C. Lange, and C. Westenfelder, “Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms,” American Journal of Physiology. Renal Physiology, vol. 289, no. 1, pp. F31–F42, 2005. View at: Publisher Site | Google Scholar
  36. H. Tsuda, K. Yamahara, K. Otani et al., “Transplantation of allogenic fetal membrane-derived mesenchymal stem cells protects against ischemia/reperfusion-induced acute kidney injury,” Cell Transplantation, vol. 23, no. 7, pp. 889–899, 2014. View at: Publisher Site | Google Scholar
  37. J. B. Zhang, X. Q. Wang, G. L. Lu, H. S. Huang, and S. Y. Xu, “Adipose-derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia-reperfusion in a rat model,” Clinical and Experimental Pharmacology & Physiology, vol. 44, no. 12, pp. 1232–1240, 2017. View at: Publisher Site | Google Scholar
  38. J. I. N. G.-J. I. E. ZHAO, J. U. N.-L. I. LIU, L. I. N. G. LIU, and H. O. N. G.-Y. I. N. G. JIA, “Protection of mesenchymal stem cells on acute kidney injury,” Molecular Medicine Reports, vol. 9, no. 1, pp. 91–96, 2014. View at: Publisher Site | Google Scholar
  39. W. Zhuo, L. Liao, Y. Fu et al., “Efficiency of endovenous versus arterial administration of mesenchymal stem cells for ischemia-reperfusion-induced renal dysfunction in rats,” Transplantation Proceedings, vol. 45, no. 2, pp. 503–510, 2013. View at: Publisher Site | Google Scholar
  40. I. H. Song, K. J. Jung, T. J. Lee et al., “Mesenchymal stem cells attenuate adriamycin-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of the NF-kB,” Nephrology (Carlton), vol. 23, no. 5, pp. 483–492, 2018. View at: Publisher Site | Google Scholar
  41. M. A. de Godoy, L. M. Saraiva, L. R. P. de Carvalho et al., “Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers,” The Journal of Biological Chemistry, vol. 293, no. 6, pp. 1957–1975, 2018. View at: Publisher Site | Google Scholar
  42. H.-H. Chang, S.-P. Hsu, and C.-T. Chien, “Intrarenal Transplantation of Hypoxic Preconditioned Mesenchymal Stem Cells Improves Glomerulonephritis through Anti-Oxidation, Anti-ER Stress, Anti-Inflammation, Anti-Apoptosis, and Anti-Autophagy,” Antioxidants, vol. 9, no. 1, p. 2, 2020. View at: Publisher Site | Google Scholar

Copyright © 2020 Tianbiao Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder
Views297
Downloads330
Citations

Related articles

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.