Cited by 139Mesenchymal stem cell researchHematopoietic Stem Cell TransplantationPeriodontal Regeneration and Treatments

Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo

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Chinnadurai, Raghavan, Garcia, Marco A., Sakurai, Yumiko, Lam, Wilbur A., Kirk, Allan D., Galipeau, Jacques, Copland, Ian B.·2014·Stem Cell Reports

Abstract

Mesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawing defect also impacts the postinfusion biodistribution properties of MSCs. Under both static and physiologic flow, compared with live MSCs in active culture, MSCs thawed from cryopreservation bound poorly to fibronectin (40% reduction) and human endothelial cells (80% reduction), respectively. This reduction correlated with a reduced cytoskeletal F-actin content in post-thaw MSCs (60% reduction). In vivo, live human MSCs could be detected in murine lung tissues for up to 24 hr, whereas thawed MSCs were undetectable. Similarly, live MSCs whose actin cytoskeleton was chemically disrupted were undetectable at 24 hr postinfusion. Our data suggest that post-thaw cryopreserved MSCs are distinct from live MSCs. This distinction could significantly affect the utility of MSCs as a cellular therapeutic.

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Crossref · 10.1016/j.stemcr.2014.05.003

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  • Cryopreservation and subsequent thawing may stunt MSC potency, immunosuppressive properties, post-infusion biodistribution, engraftment, and clearance kinetics.

    “The cryopreservation and subsequent thawing are other challenges in developing high-quality MSCs for clinical use, for they may stunt MSC potency, immunosuppressive properties, post-infusion biodistribution, engraftment, and clearance kinetics [336, 337].”

    From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [336]

    The Discussion reports reduced post-thaw immunosuppressive capacity, potential therapeutic potency, and binding and engraftment; the Results show reduced lung engraftment of thawed MSCs at 24 hours. The paper also examines post-infusion biodistribution, but it does not establish how cryopreservation changes clearance kinetics relative to live MSCs. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Authors
Chinnadurai, R., Garcia, M. A., Sakurai, Y., Lam, W. A., Kirk, A. D., Galipeau, J., & Copland, I. B.
Affiliations
  • Emory University (US)
  • Emory Healthcare (US)
  • Georgia Institute of Technology (US)
Corresponding author
Copland, Ian B.
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2014-07
Volume
3
Issue
1
Pages
60-72
ISSN
2213-6711 (ISSN-L)
OpenAlex
W2063790968
Cited by
139
References
51
Citations by year
2026: 10 · 2025: 8 · 2024: 13 · 2023: 12 · 2022: 12 · 2021: 10 · 2020: 13 · 2019: 13 · 2018: 9 · 2017: 14 · 2016: 15 · 2015: 8 · 2014: 2
FWCI
6.52
Type
journal article
Language
en
Open access
Locations
  • Stem Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Georgia Cancer Coalition
  • Emory University (P30CA138292)
  • Immune Tolerance Network (N01 AI15416)
  • National Institutes of Health (n01ai15416-28-0-11, N01-AI-15416)
  • Winship Cancer Institute (P30-CA138292)
  • National Cancer Institute (P30CA138292)
  • National Institute of Allergy and Infectious Diseases (N01 AI 15416, N01-AI-015416)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
mesenchymal stem cells, cryopreservation, actin cytoskeleton, F-actin, cell thawing, cell biodistribution, cell adhesion, fibronectin, endothelial cells, cell therapy
MeSH terms
Actins, Animals, Cell Survival, Cells, Cultured, Cytoskeleton, Female, Flow Cytometry, Humans, Male, Cryopreservation, Mice, Mesenchymal Stem Cells, Real-Time Polymerase Chain Reaction

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