Evidence map›Paper›PMID 31513644›Full record

ArticlePloS one2019

Human mesenchymal stromal cells ameliorate complement induced inflammatory cascade and improve renal functions in a rat model of ischemia-reperfusion induced acute kidney injury.

Shani Zilberman-Itskovich, Ramzia Abu-Hamad, Rina Zarura, Marina Sova, Yafit Hachmo, Moshe Stark, Sara Neuman, Shimon Slavin, Shai Efrati

Abstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shani Zilberman-ItskovichNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.ORCID 0000-0002-9289-4392
Ramzia Abu-HamadNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
Rina ZaruraNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
Marina SovaNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
Yafit HachmoNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
Moshe StarkNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
Sara NeumanBiotherapy International, The Center for Innovative Cancer Immunotherapy & Regenerative Medicine, Weizmann Center, Tel Aviv, Israel.
Shimon SlavinBiotherapy International, The Center for Innovative Cancer Immunotherapy & Regenerative Medicine, Weizmann Center, Tel Aviv, Israel.
Shai EfratiNephrology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe primary rational for using mesenchymal stromal cells (MSCs) to rejuvenate damaged tissue is mostly based on their capacity to trans-differentiate and repair injured organs. However, previous studies have demonstrated that MSCs are beneficial even at very early stages, before differentiation and proliferation can be expected. The aim of the current study was to investigate the multifaceted immunological effects of systemically administrating MSCs in the setting of acute kidney injury (AKI) induced by ischemic-reperfusion (I/R).

methodsA rat model of I/R induced AKI was used. The rats underwent a unilateral nephrectomy with simultaneously clamping the contralateral kidney for 60 minutes. Four treatment groups received intravenously, increasing doses of human MSCs and after 48 hours, the rats were sacrificed. Blood was taken to evaluate renal functions and to measure systemic inflammatory markers. Kidneys were taken for histopathologic examinations and evaluations of intra-renal complement activation and inflammatory mediators.

resultsRenal functions improved in U shaped dose dependent manner. Mean serum creatinine levels were 4.5, 2.9, 2.6, 1.7 and 4.1 mg/dL in I/R + placebo, I/R + 150x103 cells, I/R + 250x103 cells, I/R + 500x103 cells and I/R + 1,000x103 cells respectfully (p-values<0.05). Urea demonstrated consistent results with the same U shape improvement manner. The extensive activation of the complement system was ameliorated in the MSCs treatment groups. In addition, MSCs significantly decreased intra-renal levels of IL-1β and TNF-α. It should be noted that the highest doses of MSCs induced renal hypoxia, marked by the Hypoxy-probe staining.

conclusionsThe early beneficial effect of MSCs in the setting of AKI may be attributed to their immunomodulatory effects. Safe treatment with MSCs can block the deleterious activation of the complement cascade and alleviate the hazardous inflammatory mediator-related cascade.

Indexed as

Acute Kidney InjuryAnimalsComplement ActivationDisease Models, AnimalHumansInflammationKidneyMaleMesenchymal Stem CellsMesenchymal Stem Cell TransplantationRatsRats, Sprague-DawleyReperfusion Injury

Identifiers

PMID31513644
PMCPMC6741994

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.