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

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 expr...

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Bibliographic Details
Published in:Clinical and Translational Science
Main Authors: Maria Berg von Linde, Karin Johansson, Robert Kruse, Gisela Helenius, Ninos Samano, Örjan Friberg, Anne Mette Frøbert, Ole Fröbert
Format: Article in Journal/Newspaper
Language:English
Published: Wiley 2021
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Online Access:https://doi.org/10.1111/cts.12872
https://doaj.org/article/d7a00a6991174ba6a4734cfe24b39675
Description
Summary: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.