Evidence map›Paper›PMID 24805247›Full record

ArticleStem cells (Dayton, Ohio)2014

Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties?

Guido Moll, Jessica J Alm, Lindsay C Davies, Lena von Bahr, Nina Heldring, Lillemor Stenbeck-Funke, Osama A Hamad, Robin Hinsch, Lech Ignatowicz, Matthew Locke and 6 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03692221 (Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease), which is not on this map. Cited by 190 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed, 5 pooled it
13.9field-weighted citation impact, top 1% 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.

NCT03692221 early_phase1withdrawnnot on this mapstarted 2019, after this paper: background citation

Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease

TypeinterventionalSponsorUniversity Hospitals Cleveland Medical CenterRan2019 to 2022Enrolled0ConditionsDisc DegenerationArmsMSC Treatment group 1 (low dose), MSC Treatment group 2 (high dose), Healthy Control (no treatment)
3 · Its place in the literature

Who cites it

190 citing papers in PubMed, 5 syntheses or guidelines pooled it, 404 citations in OpenAlex.

  1. Pooled it
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  6. Trial
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  8. Cell Sheet Technology as a Platform for Functional Regeneration.International journal of molecular sciences · 2026
    Review
  9. Article
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  12. Article
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  15. Article
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  20. Mesenchymal stromal cell therapy: Progress to date and future outlook.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review

130 more citing papers are in PubMed but not listed here.

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

16 authors at 5 institutions in 4 countries.

Guido MollDivision of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Hematology and Regenerative Medicine Centre at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Jessica J Alm
Lindsay C Davies
Lena von Bahr
Nina Heldring
Lillemor Stenbeck-Funke
Osama A Hamad
Robin Hinsch
Lech Ignatowicz
Matthew Locke
Helena Lönnies
John D Lambris
Yuji Teramura
Kristina Nilsson-Ekdahl
Bo Nilsson
Katarina Le Blanc
Karolinska University Hospital · SEUppsala University · SEKarolinska Institutet · SECardiff University · GBUniversity of Pennsylvania · US

Funding

Role of complement in kidney disorders: from hemodialysis to transportationP01AI068730 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2007 to 2018
$16.0M
Innate immunity in clinical islet transplantation: a clinical study (CIT0-01) in U01AI065192 · NIAID · UPPSALA UNIVERSITY · PI KORSGREN, OLLE · 2004 to 2012
$11.1M
STRUCTURAL-FUNCTIONAL ANALYSIS OF COMPSTATINR01GM062134 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2001 to 2010
$2.5M
Medical Research CouncilNIAID NIH HHS 2U01AI065192-06NIAID NIH HHS AI-068730NIAID NIH HHS P01 AI068730NIAID NIH HHS U01 AI065192NIGMS NIH HHS GM-62134NIGMS NIH HHS R01 GM062134
6 · The paper itself

Abstract

We have recently reported that therapeutic mesenchymal stromal cells (MSCs) have low engraftment and trigger the instant blood mediated inflammatory reaction (IBMIR) after systemic delivery to patients, resulting in compromised cell function. In order to optimize the product, we compared the immunomodulatory, blood regulatory, and therapeutic properties of freeze-thawed and freshly harvested cells. We found that freeze-thawed MSCs, as opposed to cells harvested from continuous cultures, have impaired immunomodulatory and blood regulatory properties. Freeze-thawed MSCs demonstrated reduced responsiveness to proinflammatory stimuli, an impaired production of anti-inflammatory mediators, increased triggering of the IBMIR, and a strong activation of the complement cascade compared to fresh cells. This resulted in twice the efficiency in lysis of thawed MSCs after 1 hour of serum exposure. We found a 50% and 80% reduction in viable cells with freshly detached as opposed to thawed in vitro cells, indicating a small benefit for fresh cells. In evaluation of clinical response, we report a trend that fresh cells, and cells of low passage, demonstrate improved clinical outcome. Patients treated with freshly harvested cells in low passage had a 100% response rate, twice the response rate of 50% observed in a comparable group of patients treated with freeze-thawed cells at higher passage. We conclude that cryobanked MSCs have reduced immunomodulatory and blood regulatory properties directly after thawing, resulting in faster complement-mediated elimination after blood exposure. These changes seem to be paired by differences in therapeutic efficacy in treatment of immune ailments after hematopoietic stem cell transplantation.

Indexed as

AdolescentAdultAgedCell DifferentiationCell ProliferationCells, CulturedChildChild, PreschoolCryopreservationFemaleHumansImmunomodulationImmunophenotypingImmunotherapyInfantMaleBone marrow stromal cellsCellular therapyClinical translationCryopreservationEngraftmentImmunotherapyInstant blood-mediated inflammatory reaction

Identifiers

PMID24805247
PMCPMC4381870
OpenAlexW2116259052

What OpenQuestion holds

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LicenceTDM
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.