Evidence map›Paper›PMID 25174586›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014

Neovascularization capacity of mesenchymal stromal cells from critical limb ischemia patients is equivalent to healthy controls.

Hendrik Gremmels, Martin Teraa, Paul Ha Quax, Krista den Ouden, Joost O Fledderus, Marianne C Verhaar

Registry-linked trialOpen access · bronzeAbstract readComparative Study
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03042572 (Allogeneic Mesenchymal Stromal Cells for Angiogenesis and Neovascularization in No-option Ischemic Limbs; A Double-blind, Randomized, Placebo-controlled Trial), which is not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 7% 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.

NCT03042572 phase2 / phase3unknown statusnot on this mapstarted 2018, after this paper: background citation

Allogeneic Mesenchymal Stromal Cells for Angiogenesis and Neovascularization in No-option Ischemic Limbs; A Double-blind, Randomized, Placebo-controlled Trial

TypeinterventionalSponsorMartin Teraa, MD, PhDRan2018 to 2021Enrolled60ConditionsPeripheral Arterial Disease, Cardiovascular Diseases, Vascular DiseasesArmsAllogeneic Mesenchymal Stromal Cell, Placebo
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.

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  17. Process data of allogeneic ex vivo-expanded ABCB5Stem cell research & therapy · 2020
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  18. Mesenchymal Stem Cells Decrease M1/M2 Ratio and Alleviate Inflammation to Improve Limb Ischemia in Mice.Medical science monitor : international medical journal of experimental and clinical research · 2020
    Article
  19. Temporal changes guided by mesenchymal stem cells on a 3D microgel platform enhance angiogenesis in vivo at a low-cell dose.Proceedings of the National Academy of Sciences of the United States of America · 2020
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  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Hendrik GremmelsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Martin Teraa1] Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands [2] Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Paul Ha Quax1] Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands [2] Einthoven Laboratory of Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Krista den OudenDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Joost O FledderusDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Marianne C VerhaarDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
University Medical Center Utrecht · NLLeiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Critical limb ischemia (CLI) is often poorly treatable by conventional management and alternatives such as autologous cell therapy are increasingly investigated. Whereas previous studies showed a substantial impairment of neovascularization capacity in primary bone-marrow (BM) isolates from patients, little is known about dysfunction in patient-derived BM mesenchymal stromal cells (MSCs). In this study, we have compared CLI-MSCs to healthy controls using gene expression profiling and functional assays for differentiation, senescence and in vitro and in vivo pro-angiogenic ability. Whereas no differentially expressed genes were found and adipogenic and osteogenic differentiation did not significantly differ between groups, chondrogenic differentiation was impaired in CLI-MSCs, potentially as a consequence of increased senescence. Migration experiments showed no differences in growth factor sensitivity and secretion between CLI- and control MSCs. In a murine hind-limb ischemia model, recovery of perfusion was enhanced in MSC-treated mice compared to vehicle controls (71 ± 24% versus 44 ± 11%; P < 1 × 10(-6)). CLI-MSC- and control-MSC-treated animals showed nearly identical amounts of reperfusion (ratio CLI:Control = 0.98, 95% CI = 0.82-1.14), meeting our criteria for statistical equivalence. The neovascularization capacity of MSCs derived from CLI-patients is not compromised and equivalent to that of control MSCs, suggesting that autologous MSCs are suitable for cell therapy in CLI patients.

Indexed as

Neovascularization, PhysiologicAnimalsCell DifferentiationCells, CulturedCellular SenescenceDisease Models, AnimalGene Expression ProfilingHealthy VolunteersHumansIschemiaLegMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMice

Identifiers

PMID25174586
PMCPMC4429738
OpenAlexW2057926047

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.