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Cited by 84Mesenchymal stem cell researchAsthma and respiratory diseasesMast cells and histamine

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Freshly Thawed and Continuously Cultured Human Bone Marrow-Derived Mesenchymal Stromal Cells Comparably Ameliorate Allergic Airways Inflammation in Immunocompetent Mice

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Cruz, Fernanda F., Borg, Zachary D., Goodwin, Meagan, Sokocevic, Dino, Wagner, Darcy, McKenna, David H., Rocco, Patricia R.M., Weiss, Daniel J.·2015·Stem Cells Translational Medicine
DOI 10.5966/sctm.2014-0268PMC PMC4449099
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Abstract

Recent data suggest that freshly thawed previously frozen mesenchymal stromal cells (MSCs) may not have the same effectiveness or breadth of anti-inflammatory activities as do continuously cultured MSCs. This has significant implications for clinical use, in which many infusion schemes use frozen cells thawed at the bedside for administration. The available data, however, predominantly evaluate in vitro MSC properties, and so far there has been limited in vivo analysis. To further assess this issue, we compared freshly thawed (thawed) versus continuously cultured (fresh) human bone marrow-derived MSC (hMSC) administration in a mouse model of mixed Th2/Th17 allergic airway inflammation induced by Aspergillus hyphal extract (AHE) exposures in immunocompetent C57Bl/6 mice. Control cell populations included fresh versus thawed murine bone marrow-derived MSCs (mMSCs) and human lung fibroblasts (HLFs). Systemic administration of both thawed and fresh hMSCs and mMSCs, but not HLFs, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyper-reactivity, lung inflammation, and antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, there was no difference in effects of fresh versus thawed hMSCs or mMSCs on any outcome measured except for some variability in the effects on the bronchoalveolar lavage fluid composition. These results demonstrated potent xenogeneic effects of human MSCs in an immunocompetent mouse model of allergic airways inflammation and that thawed MSCs are as effective as fresh MSCs. The question of fresh versus thawed MSC effectiveness needs to be investigated carefully and may differ in different in vivo disease-specific models.Significance: This study addressed whether freshly thawed mesenchymal stromal cells (MSCs) are as effective in in vivo settings as those that have been continuously cultured. It also provided further data demonstrating that xenogeneic use of MSCs in immunocompetent mice is as effective as murine MSCs. This information provides further support and direction for potential clinical use of MSCs in patients with severe asthma.

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  • The impact of cryopreservation and thawing on MSC biology is still contentious, as some studies revealed no significant effect on MSC traits, including differentiation potential, phenotype, immunomodulatory properties, and lack of malignant transformation.

    “Nevertheless, the impact of cryopreservation and thawing on MSC biology is still contentious, as some studies revealed no significant effect on MSC traits, including differentiation potential, phenotype, immunomodulatory properties, and lack of malignant transformation [338, 339].”

    From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [338]

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Research works printed but not linked: 47

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Metadata

Authors
Cruz, F. F., Borg, Z. D., Goodwin, M., Sokocevic, D., Wagner, D., McKenna, D. H., Rocco, P. R. M., & Weiss, D. J.
Affiliations
  • University of Vermont (US)
  • University of Minnesota (US)
  • Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Corresponding author
Weiss, Daniel J.
ORCID
Venue
Stem Cells Translational Medicine
Publisher
Oxford University Press (OUP)
Published
2015-04-29
Volume
4
Issue
6
Pages
615-624
ISSN
  • 2157-6564 (ISSN-L)
  • 2157-6580
DOI
10.5966/sctm.2014-0268
PMC
PMC4449099
OpenAlex
W2145815234
Cited by
84
References
49
Citations by year
2026: 1 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 13 · 2019: 10 · 2018: 5 · 2017: 9 · 2016: 14 · 2015: 2
FWCI
5.60
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Stem Cells Translational Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • NIH American Recovery and Reinvestment Act (RC4HL106625)
  • National Heart, Lung, and Blood Institute (R21HL108689)
  • Vermont Lung Center of Biomedical Research Excellence (P20RR15557)
  • NIH Production Assistance for Cellular Therapies (HHSN268201000008C)
  • NIH/National Center for Research Resources (P40RR017447)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
Keywords
mesenchymal stem cells, bone marrow-derived mesenchymal stromal cells, cell thawing, frozen cell storage, continuous cell culture, allergic airway inflammation, airway hyperresponsiveness, immunocompetent mice, severe asthma, cell therapy
MeSH terms
Animals, Asthma, Bone Marrow Cells, Disease Models, Animal, Humans, Cryopreservation, Th2 Cells, Mesenchymal Stem Cell Transplantation, Mice, Th17 Cells, Mesenchymal Stem Cells, Heterografts

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