Differences in the Inflammatory Response of White Adipose Tissue and Adipose-Derived Stem Cells

被引:9
作者
Taha, Sara [1 ,2 ]
Volkmer, Elias [1 ,3 ]
Haas, Elisabeth [1 ,2 ]
Alberton, Paolo [1 ]
Straub, Tobias [4 ]
David-Rus, Diana [5 ]
Aszodi, Attila [1 ]
Giunta, Riccardo [2 ]
Saller, Maximilian Michael [1 ]
机构
[1] Ludwig Maximilians Univ Munchen, Dept Gen Trauma & Reconstruct Surg, Expt Surg & Regenerat Med ExperiMed, Fraunhoferstr 20, D-82152 Planegg Martinsried, Germany
[2] Ludwig Maximilians Univ Munchen, Div Hand Plast & Aesthet Surg, Pettenkoferstr 8a, D-80336 Munich, Germany
[3] Helios Klinikum Munchen West, Dept Hand Surg, Steinerweg 5, D-81241 Munich, Germany
[4] Ludwig Maximilians Univ Munchen, Biomed Ctr Munich, Bioinformat Unit, Grosshaderner Str 9, D-82152 Planegg Martinsried, Germany
[5] Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol IBE, Marchioninistr 15, D-81377 Munich, Germany
关键词
white fat tissue; adipose-derived stem cells; immunomodulation; inflammation; TNFalpha; STROMAL CELLS; CYTOKINES; CARTILAGE; IL-4; FAT; OSTEOARTHRITIS; REGENERATION; MECHANISMS; BIOLOGY;
D O I
10.3390/ijms21031086
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The application of liposuctioned white adipose tissue (L-WAT) and adipose-derived stem cells (ADSCs) as a novel immunomodulatory treatment option is the currently subject of various clinical trials. Because it is crucial to understand the underlying therapeutic mechanisms, the latest studies focused on the immunomodulatory functions of L-WAT or ADSCs. However, studies that examine the specific transcriptional adaptation of these treatment options to an extrinsic inflammatory stimulus in an unbiased manner are scarce. The aim of this study was to compare the gene expression profile of L-WAT and ADSCs, when subjected to tumor necrosis factor alpha (TNF alpha), and to identify key factors that might be therapeutically relevant when using L-WAT or ADSCs as an immuno-modulator. Fat tissue was harvested by liposuction from five human donors. ADSCs were isolated from the same donors and shortly subjected to expansion culture. L-WAT and ADSCs were treated with human recombinant TNF alpha, to trigger a strong inflammatory response. Subsequently, an mRNA deep next-generation sequencing was performed to evaluate the different inflammatory responses of L-WAT and ADSCs. We found significant gene expression changes in both experimental groups after TNF alpha incubation. However, ADSCs showed a more homogenous gene expression profile by predominantly expressing genes involved in immunomodulatory processes such as CCL19, CCL5, TNFSF15 and IL1 beta when compared to L-WAT, which reacted rather heterogeneously. As RNA sequencing between L-WAT and ADSCS treated with TNF alpha revealed that L-WAT responded very heterogeneously to TNF alpha treatment, we therefore conclude that ADSCs are more reliable and predictable when used therapeutically. Our study furthermore yields insight into potential biological processes regarding immune system response, inflammatory response, and cell activation. Our results can help to better understand the different immunomodulatory effects of L-WAT and ADSCs.
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页数:14
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