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Expression of Paracrine Effectors in Human Adipose-Derived Mesenchymal Stem Cells Treated With Plasma From Brown Bears (Ursus arctos)

Berg von Linde, Maria LU ; Johansson, Karin ; Kruse, Robert ; Helenius, Gisela ; Samano, Ninos ; Friberg, Örjan ; Frøbert, Anne Mette and Fröbert, Ole (2021) In Clinical and Translational Science 14(1). p.317-325
Abstract

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for novel cell therapeutic applications. Hibernating brown bears sustain tissue integrity and function via unknown mechanisms, which might be plasma borne. We hypothesized that plasma from hibernating bears may increase the expression of favorable factors from human ADSCs. In an experimental study, ADSCs from patients with ischemic heart disease were treated with interventional media containing plasma from hibernating and active bears, respectively, and with control medium. Extracted RNA from the ADSCs was sequenced using next generation sequencing. Statistical analyses of differentially expressed genes were performed using fold change analysis, pathway analysis,... (More)

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for novel cell therapeutic applications. Hibernating brown bears sustain tissue integrity and function via unknown mechanisms, which might be plasma borne. We hypothesized that plasma from hibernating bears may increase the expression of favorable factors from human ADSCs. In an experimental study, ADSCs from patients with ischemic heart disease were treated with interventional media containing plasma from hibernating and active bears, respectively, and with control medium. Extracted RNA from the ADSCs was sequenced using next generation sequencing. Statistical analyses of differentially expressed genes were performed using fold change analysis, pathway analysis, and gene ontology. As a result, we found that genes associated with inflammation, such as IGF1, PGF, IL11, and TGFA, were downregulated by > 10-fold in ADSCs treated with winter plasma compared with control. Genes important for cardiovascular development, ADM, ANGPTL4, and APOL3, were upregulated in ADSCs when treated with winter plasma compared with summer plasma. ADSCs treated with bear plasma, regardless if it was from hibernating or active bears, showed downregulation of IGF1, PGF, IL11, INHBA, IER3, and HMOX1 compared with control, suggesting reduced cell growth and differentiation. This can be summarized in the conclusion that plasma from hibernating bears suppresses inflammatory genes and activates genes associated with cardiovascular development in human ADSCs. Identifying the involved regulator(s) holds therapeutic potential.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Aged, Aged, 80 and over, Animals, Cell Differentiation/immunology, Cells, Cultured, Coronary Artery Bypass, Culture Media/metabolism, Female, Hibernation/immunology, Humans, Male, Mesenchymal Stem Cell Transplantation/methods, Mesenchymal Stem Cells/immunology, Myocardial Ischemia/immunology, Plasma/immunology, Primary Cell Culture/methods, Seasons, Subcutaneous Fat/cytology, Transplantation, Autologous/methods, Ursidae/blood
in
Clinical and Translational Science
volume
14
issue
1
pages
317 - 325
publisher
Wiley-Blackwell
external identifiers
  • scopus:85091017319
  • pmid:32949228
ISSN
1752-8062
DOI
10.1111/cts.12872
language
English
LU publication?
no
additional info
© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
id
f3ddf3fa-5df4-498b-b7c7-c619c24fa262
date added to LUP
2023-02-02 10:08:50
date last changed
2024-03-21 08:13:26
@article{f3ddf3fa-5df4-498b-b7c7-c619c24fa262,
  abstract     = {{<p>Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for novel cell therapeutic applications. Hibernating brown bears sustain tissue integrity and function via unknown mechanisms, which might be plasma borne. We hypothesized that plasma from hibernating bears may increase the expression of favorable factors from human ADSCs. In an experimental study, ADSCs from patients with ischemic heart disease were treated with interventional media containing plasma from hibernating and active bears, respectively, and with control medium. Extracted RNA from the ADSCs was sequenced using next generation sequencing. Statistical analyses of differentially expressed genes were performed using fold change analysis, pathway analysis, and gene ontology. As a result, we found that genes associated with inflammation, such as IGF1, PGF, IL11, and TGFA, were downregulated by &gt; 10-fold in ADSCs treated with winter plasma compared with control. Genes important for cardiovascular development, ADM, ANGPTL4, and APOL3, were upregulated in ADSCs when treated with winter plasma compared with summer plasma. ADSCs treated with bear plasma, regardless if it was from hibernating or active bears, showed downregulation of IGF1, PGF, IL11, INHBA, IER3, and HMOX1 compared with control, suggesting reduced cell growth and differentiation. This can be summarized in the conclusion that plasma from hibernating bears suppresses inflammatory genes and activates genes associated with cardiovascular development in human ADSCs. Identifying the involved regulator(s) holds therapeutic potential.</p>}},
  author       = {{Berg von Linde, Maria and Johansson, Karin and Kruse, Robert and Helenius, Gisela and Samano, Ninos and Friberg, Örjan and Frøbert, Anne Mette and Fröbert, Ole}},
  issn         = {{1752-8062}},
  keywords     = {{Aged; Aged, 80 and over; Animals; Cell Differentiation/immunology; Cells, Cultured; Coronary Artery Bypass; Culture Media/metabolism; Female; Hibernation/immunology; Humans; Male; Mesenchymal Stem Cell Transplantation/methods; Mesenchymal Stem Cells/immunology; Myocardial Ischemia/immunology; Plasma/immunology; Primary Cell Culture/methods; Seasons; Subcutaneous Fat/cytology; Transplantation, Autologous/methods; Ursidae/blood}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{317--325}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Clinical and Translational Science}},
  title        = {{Expression of Paracrine Effectors in Human Adipose-Derived Mesenchymal Stem Cells Treated With Plasma From Brown Bears (Ursus arctos)}},
  url          = {{http://dx.doi.org/10.1111/cts.12872}},
  doi          = {{10.1111/cts.12872}},
  volume       = {{14}},
  year         = {{2021}},
}