Individual immune cell and cytokine profiles determine platelet-rich plasma composition

Arthritis Research & Therapy

Research

Luis Lauterbach¹  Georg N. Duda¹  Simon Reinke¹  Sven Geißler¹  Gerald Grütz¹  Antje Blankenstein¹  Andreas Wilhelm¹  Melanie Ort²  Ulrich Stöckle³  Carsten Perka³  Marcel Niemann⁴  Frank Graef⁴  Tobias Winkler⁵  Tazio Maleitzke⁶  Florian N. Fleckenstein⁷  Mathias Streitz⁸ 

[1] Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Augustenburger Platz 1, 13353, Berlin, Germany;Department of Biology, Chemistry and Pharmacy, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195, Berlin, Germany;Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353, Berlin, Germany;Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Augustenburger Platz 1, 13353, Berlin, Germany;Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany;Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany;Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Diagnostic and Interventional Radiology, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany;Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald, Insel Riems, Germany;

关键词: Osteoarthritis;    Inflammation;    Orthobiologics;    Regenerative therapies;    Immune system;   

DOI  :  10.1186/s13075-022-02969-6

 received in 2022-05-03, accepted in 2022-12-02,  发布年份 2022

来源: Springer

【 摘 要 】

ObjectivePlatelet-rich plasma (PRP) therapy is increasingly popular to treat musculoskeletal diseases, including tendinopathies and osteoarthritis (OA). To date, it remains unclear to which extent PRP compositions are determined by the immune cell and cytokine profile of individuals or by the preparation method. To investigate this, we compared leukocyte and cytokine distributions of different PRP products to donor blood samples and assessed the effect of pro-inflammatory cytokines on chondrocytes.DesignFor each of three PRP preparations (ACP®, Angel™, and nSTRIDE® APS), products were derived using whole blood samples from twelve healthy donors. The cellular composition of PRP products was analyzed by flow cytometry using DURAClone antibody panels (DURAClone IM Phenotyping Basic and DURAClone IM T Cell Subsets). The MESO QuickPlex SQ 120 system was used to assess cytokine profiles (V-PLEX Proinflammatory Panel 1 Human Kit, Meso Scale Discovery). Primary human chondrocyte 2D and 3D in vitro cultures were exposed to recombinant IFN-γ and TNF-α. Proliferation and chondrogenic differentiation were quantitatively assessed.ResultsAll three PRP products showed elevated portions of leukocytes compared to baseline levels in donor blood. Furthermore, the pro-inflammatory cytokines IFN-γ and TNF-α were significantly increased in nSTRIDE® APS samples compared to donor blood and other PRP products. The characteristics of all other cytokines and immune cells from the donor blood, including pro-inflammatory T cell subsets, were maintained in all PRP products. Chondrocyte proliferation was impaired by IFN-γ and enhanced by TNF-α treatment. Differentiation and cartilage formation were compromised upon treatment with both cytokines, resulting in altered messenger ribonucleic acid (mRNA) expression of collagen type 1A1 (COL1A1), COL2A1, and aggrecan (ACAN) as well as reduced proteoglycan content.ConclusionsIndividuals with elevated levels of cells with pro-inflammatory properties maintain these in the final PRP products. The concentration of pro-inflammatory cytokines strongly varies between PRP products. These observations may help to unravel the previously described heterogeneous response to PRP in OA therapy, especially as IFN-γ and TNF-α impacted primary chondrocyte proliferation and their characteristic gene expression profile. Both the individual’s immune profile and the concentration method appear to impact the final PRP product.Trial registrationThis study was prospectively registered in the Deutsches Register Klinischer Studien (DRKS) on 4 November 2021 (registration number DRKS00026175).

【 授权许可】

CC BY   
© The Author(s) 2023

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