Individual immune cell and cytokine profiles determine platelet-rich plasma composition
Abstract Objective Platelet-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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-01-01
|
| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02969-6 |
| _version_ | 1797952416552845312 |
|---|---|
| author | Marcel Niemann Melanie Ort Luis Lauterbach Mathias Streitz Andreas Wilhelm Gerald Grütz Florian N. Fleckenstein Frank Graef Antje Blankenstein Simon Reinke Ulrich Stöckle Carsten Perka Georg N. Duda Sven Geißler Tobias Winkler Tazio Maleitzke |
| author_facet | Marcel Niemann Melanie Ort Luis Lauterbach Mathias Streitz Andreas Wilhelm Gerald Grütz Florian N. Fleckenstein Frank Graef Antje Blankenstein Simon Reinke Ulrich Stöckle Carsten Perka Georg N. Duda Sven Geißler Tobias Winkler Tazio Maleitzke |
| author_sort | Marcel Niemann |
| collection | DOAJ |
| description | Abstract Objective Platelet-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. Design For 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. Results All 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. Conclusions Individuals 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 registration This study was prospectively registered in the Deutsches Register Klinischer Studien (DRKS) on 4 November 2021 (registration number DRKS00026175). |
| first_indexed | 2024-04-10T22:46:00Z |
| format | Article |
| id | doaj.art-68783f4df52245348d097f107759d32b |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-10T22:46:00Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-68783f4df52245348d097f107759d32b2023-01-15T12:17:32ZengBMCArthritis Research & Therapy1478-63622023-01-0125111410.1186/s13075-022-02969-6Individual immune cell and cytokine profiles determine platelet-rich plasma compositionMarcel Niemann0Melanie Ort1Luis Lauterbach2Mathias Streitz3Andreas Wilhelm4Gerald Grütz5Florian N. Fleckenstein6Frank Graef7Antje Blankenstein8Simon Reinke9Ulrich Stöckle10Carsten Perka11Georg N. Duda12Sven Geißler13Tobias Winkler14Tazio Maleitzke15Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal SurgeryBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-InstitutBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Diagnostic and Interventional RadiologyCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal SurgeryBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal SurgeryCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal SurgeryBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff InstituteCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal SurgeryCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal SurgeryAbstract Objective Platelet-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. Design For 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. Results All 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. Conclusions Individuals 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 registration This study was prospectively registered in the Deutsches Register Klinischer Studien (DRKS) on 4 November 2021 (registration number DRKS00026175).https://doi.org/10.1186/s13075-022-02969-6OsteoarthritisInflammationOrthobiologicsRegenerative therapiesImmune system |
| spellingShingle | Marcel Niemann Melanie Ort Luis Lauterbach Mathias Streitz Andreas Wilhelm Gerald Grütz Florian N. Fleckenstein Frank Graef Antje Blankenstein Simon Reinke Ulrich Stöckle Carsten Perka Georg N. Duda Sven Geißler Tobias Winkler Tazio Maleitzke Individual immune cell and cytokine profiles determine platelet-rich plasma composition Arthritis Research & Therapy Osteoarthritis Inflammation Orthobiologics Regenerative therapies Immune system |
| title | Individual immune cell and cytokine profiles determine platelet-rich plasma composition |
| title_full | Individual immune cell and cytokine profiles determine platelet-rich plasma composition |
| title_fullStr | Individual immune cell and cytokine profiles determine platelet-rich plasma composition |
| title_full_unstemmed | Individual immune cell and cytokine profiles determine platelet-rich plasma composition |
| title_short | Individual immune cell and cytokine profiles determine platelet-rich plasma composition |
| title_sort | individual immune cell and cytokine profiles determine platelet rich plasma composition |
| topic | Osteoarthritis Inflammation Orthobiologics Regenerative therapies Immune system |
| url | https://doi.org/10.1186/s13075-022-02969-6 |
| work_keys_str_mv | AT marcelniemann individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT melanieort individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT luislauterbach individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT mathiasstreitz individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT andreaswilhelm individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT geraldgrutz individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT floriannfleckenstein individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT frankgraef individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT antjeblankenstein individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT simonreinke individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT ulrichstockle individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT carstenperka individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT georgnduda individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT svengeißler individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT tobiaswinkler individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition AT taziomaleitzke individualimmunecellandcytokineprofilesdetermineplateletrichplasmacomposition |