Evidence map›Paper›PMID 35279204›Full record

ArticleStem cell research & therapy2022

Therapeutic role of uterine-derived stem cells in acute kidney injury.

Ramanaiah Mamillapalli, SiHyun Cho, Levent Mutlu, Hugh S Taylor

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 46% of its field
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

5 citing papers in PubMed, 5 citations in OpenAlex.

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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

4 authors at 1 institution in 2 countries.

Ramanaiah Mamillapalli *Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 310 Cedar Street, New Haven, CT, 06510, USA. ramana.mamillapalli@yale.edu.ORCID 0000-0002-4022-8910
SiHyun Cho *Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 310 Cedar Street, New Haven, CT, 06510, USA.
Levent Mutlu *Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 310 Cedar Street, New Haven, CT, 06510, USA.
Hugh S TaylorDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 310 Cedar Street, New Haven, CT, 06510, USA.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Environmental Estrogen Induced Epigenetic Alteration of Uterine Stem CellsR01HD076422 · NICHD · YALE UNIVERSITY · PI TAYLOR, HUGH SMITH · 2012 to 2016
$2.0M
NCATS NIH HHS UL1 TR001863NICHD NIH HHS R01 HD076422NIH HHS NIH R01 HD076422
6 · The paper itself

Abstract

backgroundAcute kidney injury (AKI) causes abrupt deterioration in kidney function that disrupts metabolic, electrolyte and fluid homeostasis. Although the prevalence of AKI is steadily increasing, no definitive treatment options are available, leading to severe morbidity and mortality. We evaluated the role of uterine-derived multipotent stem cells in kidney regeneration after ischemic AKI.

methodsFemale C57BL/6J mice were hysterectomized and subsequently subject to AKI by either unilateral or bilateral renal ischemia-reperfusion injury. Uterine-derived cells (UDCs), containing a population of uterine stem cells, were isolated from the uteri of female transgenic DsRed mice and injected intravenously to AKI mice. Engraftment of DsRed cells was analyzed by flow cytometry while serum creatinine levels were determined colorimetrically. Expression of UDC markers and cytokine markers were analyzed by immunohistochemical and qRT-PCR methods, respectively. The Kaplan-Meier method was used to analyze survival time while unpaired t test with Welch's correction used for data analysis between two groups.

resultsMice with an intact uterus, and hence an endogenous source of UDCs, had a higher survival rate after bilateral ischemic AKI compared to hysterectomized mice. Mice treated with infusion of exogenous UDCs after hysterectomy/AKI had lower serum creatinine levels and higher survival rates compared to controls that did not receive UDCs. Engraftment of labeled UDCs was significantly higher in kidneys of bilateral ischemic AKI mice compared to those that underwent a sham surgery. When unilateral ischemic AKI was induced, higher numbers of UDCs were found in the injured than non-injured kidney. Immunofluorescence staining demonstrated double-positive DsRed/Lotus tetragonolobus agglutinin (LTA) positive cells and DsRed/CD31 positive cells indicating contribution of UDCs in renal tubular and vascular regeneration. Expression of Cxcl12, Bmp2, Bmp4, and Ctnf in renal tissue was significantly higher in the UDCs injection group than the control group.

conclusionsUDCs engrafted injured kidneys, contributed to proximal tubule and vascular regeneration, improved kidney function and increased survival in AKI mice. UDC administration is a promising new therapy for AKI. Endogenous uterine stem cells likely also preserve kidney function, suggesting a novel interaction between the uterus and kidney. We suggest that hysterectomy may have a detrimental effect on response to renal injury.

Indexed as

Acute Kidney InjuryReperfusion InjuryAnimalsFemaleKidneyMiceMice, Inbred C57BLRegenerationStem CellsUterusAcute kidney injuryHysterectomyRenal functionSurvivalUterine-derived cells

Identifiers

PMID35279204
PMCPMC8917641
OpenAlexW4221118241

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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.