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Cited by 1,898Mesenchymal stem cell researchCardiac Fibrosis and RemodelingAcute Myocardial Infarction Research

Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6

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Lee, Ryang Hwa, Pulin, Andrey A., Seo, Min Jeong, Kota, Daniel J., Ylostalo, Joni, Larson, Benjamin L., Semprun-Prieto, Laura, Delafontaine, Patrice +1 more·2009·Cell Stem Cell
DOI 10.1016/j.stem.2009.05.003PMC PMC4154377
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Abstract

Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 x 10(6) hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. I.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.

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  • BM-MSCs can reduce apoptosis of resting or activated neutrophils by releasing IL-6, TSG-6 and SOD3.

    “by releasing IL-6 [42], TSG-6 [62] and superoxide dismutase (SOD3) [63], BM-MSCs can reduce apoptosis of neutrophils that are resting or activated [42]”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [62]

  • Preclinical studies and clinical trials demonstrated that MSC transplantation significantly improves liver function and is safe and effective in liver failure.

    “Preclinical studies [22–25] and clinical trials [26–30] demonstrated that MSC transplantation significantly improves liver function and is safe and effective in the treatment of liver failure.”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [24]

    The Results and Discussion concern improved cardiac outcomes after MSC infusion in mice with myocardial infarction, not liver failure. The Introduction mentions MSC clinical trials for other conditions but reports no liver-function outcomes or evidence that MSC treatment is safe and effective for liver failure. Searches for liver failure, liver function, and hepatic clinical trials found no supporting passage in our copy. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Lee, R. H., Pulin, A. A., Seo, M. J., Kota, D. J., Ylostalo, J., Larson, B. L., Semprun-Prieto, L., Delafontaine, P., & Prockop, D. J.
Affiliations
Tulane University (US)
Corresponding author
Prockop, Darwin J.
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2009-07
Volume
5
Issue
1
Pages
54-63
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2009.05.003
PMC
PMC4154377
OpenAlex
W2021916724
Cited by
1,898
References
3
Citations by year
2026: 33 · 2025: 76 · 2024: 103 · 2023: 98 · 2022: 118 · 2021: 178 · 2020: 138 · 2019: 126 · 2018: 131 · 2017: 130 · 2016: 152 · 2015: 135 · 2014: 96 · 2013: 125 · 2012: 123
FWCI
40.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (P01HL075161, HL073252, R01HL080682, R01HL073252)
  • National Center for Research Resources (P40RR017447, P40 RR 17 447)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords
human mesenchymal stem cells, myocardial infarction, TSG-6, intravenous cell transplantation, pulmonary embolism, cell engraftment, anti-inflammatory activity, cardiac inflammation, infarct size, cardiac function, paracrine signaling, siRNA knockdown
MeSH terms
Animals, Heart, Humans, Infusions, Intravenous, Lung, Myocardial Infarction, Pulmonary Embolism, Cell Adhesion Molecules, Stromal Cells, Inflammation Mediators, Gene Expression Profiling, Multipotent Stem Cells, Mice, Cell Migration Assays

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