Evidence map›Paper›PMID 40221815›Full record

ArticleStem cell research & therapy2025

Erythropoietin delivery through kidney organoids engineered with an episomal DNA vector.

Z Du, A Bas-Cristóbal Menéndez, M Urban, A Hartley, D Ratsma, M Koedam, T P P van den Bosch, M Clahsen-van Groningen, J Gribnau, J Mulder and 5 more

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In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

What it found

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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

1 citing paper in PubMed.

  1. Review
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

15 authors.

Z DuErasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center, Wytemaweg 80, Rotterdam, 3015 CN, The Netherlands.
A Bas-Cristóbal MenéndezErasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center, Wytemaweg 80, Rotterdam, 3015 CN, The Netherlands.
M UrbanDNA Vector Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany.
A HartleyDNA Vector Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany.
D RatsmaDepartment of Internal Medicine, University Medical Center, Rotterdam, The Netherlands.
M KoedamDepartment of Internal Medicine, University Medical Center, Rotterdam, The Netherlands.
T P P van den BoschDepartment of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
M Clahsen-van GroningenDepartment of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
J GribnauDepartment of Developmental Biology and iPS Core Facility, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
J MulderDepartment of Pediatrics, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands.
M E J ReindersErasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center, Wytemaweg 80, Rotterdam, 3015 CN, The Netherlands.
C C BaanErasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center, Wytemaweg 80, Rotterdam, 3015 CN, The Netherlands.
B van der EerdenDepartment of Internal Medicine, University Medical Center, Rotterdam, The Netherlands.
R P HarbottleDNA Vector Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Martin J HoogduijnErasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center, Wytemaweg 80, Rotterdam, 3015 CN, The Netherlands. m.hoogduijn@erasmusmc.nl.ORCID http://orcid.org/0000-0002-0217-8254

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe kidney's endocrine function is essential for maintaining body homeostasis. Erythropoietin (EPO) is one of the key endocrine factors produced by the kidney, and kidney disease patients frequently experience anemia due to impaired EPO production. In the present study we explored the potential of human induced pluripotent stem cell (iPSC)-derived kidney organoids to restore EPO production.

methodsEPO secretion by kidney organoids was examined under 1% and 20% oxygen levels. To increase the EPO secreting capacity of kidney organoids, iPSC were genetically engineered with a non-integrating scaffold/matrix attachment region (S/MAR) DNA vector containing the EPO gene and generated EPO-overexpressing (EPO+) kidney organoids. To assess the physiological effects of EPO + organoids, 2-8 organoids were implanted subcutaneously in immunodeficient mice.

resultsKidney organoids produced low amounts of EPO under 1% oxygen. EPO S/MAR DNA vectors persisted and continued to robustly express EPO during iPSC expansion and kidney organoid differentiation without interfering with cellular proliferation. EPO + iPSC demonstrated efficient differentiation into kidney organoids. One-month post-implantation, EPO + organoids displayed continuously elevated EPO mRNA levels and significantly increased endothelial cell numbers compared to control organoids. Hematocrit levels were notably elevated in mice implanted with EPO + organoids in an organoid number-dependent manner. EPO + organoids furthermore influenced bone homeostasis in their hosts, evidenced by a change in trabecular bone composition.

conclusionKidney organoids modified by EPO S/MAR DNA vector allow stable long-term delivery of EPO. The observed physiological effects following the implantation of EPO + organoids underscore the potential of gene-edited kidney organoids for endocrine restoration therapy.

Indexed as

ErythropoietinKidneyOrganoidsPlasmidsAnimalsCell DifferentiationGenetic VectorsHumansInduced Pluripotent Stem CellsMiceEPO protein, humanErythropoietinDNA vectorErythropoietinKidneyOrganoidsPluripotent stem cells

Identifiers

PMID40221815
PMCPMC11993987

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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.