Evidence map›Paper›PMID 39066775›Full record

ArticleCytotherapy2024

Cryopreservation of mesenchymal stem/stromal cells using a DMSO-free solution is comparable to DMSO-containing cryoprotectants: results of an international multicenter PACT/BEST collaborative study.

Theodros Mamo, Cheryl A Cox, Connor Demorest, Magali J Fontaine, Allison Hubel, Linda Kelley, Aisha Khan, Denese C Marks, Shibani Pati, Jo-Anna Reems and 7 more

Abstract readMulticenter Study
In one paragraph

Article in Cytotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–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.

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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

17 authors.

Theodros MamoDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address: mamo0016@umn.edu.
Cheryl A CoxMoffitt Cancer Center, Tampa, Florida, USA.
Connor DemorestMasonic Cancer Center Biostatistics Core, University of Minnesota, Minneapolis, Minnesota, USA.
Magali J FontaineUniversity of Maryland School of Medicine, Baltimore, Maryland, USA.
Allison HubelDepartment of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota, USA; Evia Bio, Minneapolis, Minnesota, USA.
Linda KelleyMoffitt Cancer Center, Tampa, Florida, USA.
Aisha KhanUniversity of Miami, Coral Gables, Florida, USA.
Denese C MarksResearch and Development, Australian Red Cross Lifeblood, Sydney, Australia.
Shibani PatiUniversity of California San Francisco, San Francisco, California, USA.
Jo-Anna ReemsUniversity of Utah, Salt Lake City, Utah, USA.
Gabriele SpohnGerman Red Cross Blood Donor Service and Goethe University Hospital, Frankfurt am Main, Germany.
Richard SchäferGerman Red Cross Blood Donor Service and Goethe University Hospital, Frankfurt am Main, Germany; Medical Center, Center for Chronic Immunodeficiency, University of Freiburg, Freiburg, Germany.
Rongye ShiCenter for Cellular Engineering, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Lipei ShaoCenter for Cellular Engineering, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
David StroncekCenter for Cellular Engineering, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
David H McKennaDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA; Molecular and Cellular Therapeutics, University of Minnesota, Saint Paul, Minnesota, USA.
Biomedical Excellence for Safer Transfusion (BEST) Collaborative

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
NCI NIH HHS P01 CA065493NCI NIH HHS P30 CA076292NHLBI NIH HHS HHSN268201600012CNHLBI NIH HHS HHSN268201600014CNIH HHS HHSN263201600012INIH HHS HHSN263201600014I
6 · The paper itself

Abstract

BACKGROUND AND

aimAn essential aspect of ensuring availability and stability of mesenchymal stem/stromal cells (MSCs) products for clinical use is that these cells are cryopreserved before individual infusion into patients. Currently, cryopreservation of MSCs involves use of a cryoprotectant solution containing dimethyl sulfoxide (DMSO). However, it is recognized that DMSO may be toxic for both the patient and the MSC product. In this Production Assistance for Cellular Therapies (PACT) and Biomedical Excellence for Safer Transfusion (BEST) Collaborative study, we compared a novel DMSO-free solution with DMSO containing cryoprotectant solutions for freezing MSCs.

methodsA DMSO-free cryoprotectant solution containing sucrose, glycerol, and isoleucine (SGI) in a base of Plasmalyte A was prepared at the University of Minnesota. Cryoprotectant solutions containing 5-10% DMSO (in-house) were prepared at seven participating centers (five from USA, one each from Australia and Germany). The MSCs were isolated from bone marrow or adipose tissue and cultured ex vivo per local protocols at each center. The cells in suspension were frozen by aliquoting into vials/bags. For six out of the seven centers, the vials/bags were placed in a controlled rate freezer (one center placed them at -80°C freezer overnight) before transferring to liquid nitrogen. The cells were kept frozen for at least one week before thawing and testing. Pre- and post-thaw assessment included cell viability and recovery, immunophenotype as well as transcriptional and gene expression profiles. Linear regression, mixed effects models and two-sided t-tests were applied for statistical analysis.

resultsMSCs had an average viability of 94.3% (95% CI: 87.2-100%) before cryopreservation, decreasing by 4.5% (95% CI: 0.03-9.0%; P: 0.049) and 11.4% (95% CI: 6.9-15.8%; P< 0.001), for MSCs cryopreserved in the in-house and SGI solutions, respectively. The average recovery of viable MSCs cryopreserved in the SGI was 92.9% (95% CI: 85.7-100.0%), and it was lower by 5.6% (95% CI: 1.3-9.8%, P < 0.013) for the in-house solution. Additionally, MSCs cryopreserved in the two solutions had expected level of expressions for CD45, CD73, CD90, and CD105 with no significant difference in global gene expression profiles.

conclusionMSCs cryopreserved in a DMSO-free solution containing sucrose, glycerol, and isoleucine in a base of Plasmalyte A had slightly lower cell viability, better recovery, and comparable immunophenotype and global gene expression profiles compared to MSCs cryopreserved in DMSO containing solutions. The average viability of MSCs in the novel solution was above 80% and, thus, likely clinically acceptable. Future studies are suggested to test the post-thaw functions of MSCs cryopreserved in the novel DMSO-free solution.

Indexed as

CryopreservationCryoprotective AgentsDimethyl SulfoxideMesenchymal Stem CellsCells, CulturedCell SurvivalHumansCryoprotective AgentsDimethyl SulfoxidecryopreservationcryoprotectantDMSOmesenchymal stem/stromal cells (MSCs)

Identifiers

PMID39066775
PMCPMC11841823

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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.