Effect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization

Uchiyama, Ryoka; Toyoda, Eiji; Maehara, Miki; Wasai, Shiho; Omura, Haruka; Watanabe, Masahiko; Sato, Masato

doi:10.3390/ijms22052336

Cited by 64 publications

(55 citation statements)

References 43 publications

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“…In this context, PRP molecules can influence the polarization of macrophages [39,40], producing different macrophage states and setting the basis for novel formulations specifically targeted to macrophage polarization. The present bioinformatic analysis predicts PRP intervention in macrophage biology and a role in modulating their crosstalk with other immune cells.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

Amo

Perez‐Valle

Atilano

et al. 2022

JCM

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Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely PRP and platelet-poor plasma (PPP), were prepared from six healthy donors following a biobank-automated protocol. Inter-donor differences were analyzed, and pools were created before performing multiplexing protein arrays. In addition, PRP and PPP were prepared from six patients following our in-house protocols. Supernatants from PRP and PPP were harvested one hour after calcium chloride activation. Multiplexing protein arrays were performed in parallel for all plasma formulations. Results were normalized to fold change in relation to PPP and examined using Ingenuity Pathway Analysis Software. Bioinformatic predictions showed that PRPs constitute a signaling system with interrelated networks of inflammatory and angiogenic proteins, including but not limited to interleukin-6 and -8 (IL-6, IL-8), insulin like growth factor 1 (IGF-1), transforming growth factor beta, (TGF-b), and vascular endothelial growth factor (VEGF) signaling, underlying biological actions. Predictions of canonical systems activated with PRP molecules include various inflammatory pathways, including high-mobility group box protein (HMGB1) and interleukin 17 (IL-17) signaling, neuroinflammation, and nuclear factor-kappa b (NF-κB) pathways. Eventually, according to these predictions and OA evolving knowledge, selected PRP formulations should be tailored to modulate different inflammatory phenotypes, i.e., meta-inflammation, inflame-aging or posttraumatic inflammatory osteoarthritis. However, further research to discriminate the peculiarities of autologous versus allogeneic formulations and their effects on the various OA inflammatory phenotypes is needed to foster PRPs.

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Section: Discussionmentioning

confidence: 99%

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

Amo

Perez‐Valle

Atilano

et al. 2022

JCM

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“…The polarized synovial macrophages appear to be a suitable therapeutic target for the early prevention and treatment of OA. Several in vitro studies have reported the promotion of M2 macrophages by platelet-rich plasma (PRP) [ 28 ] and mesenchymal stem cells [ 29 , 30 , 31 , 32 ]. However, few studies have evaluated the effect of human SVF or ADRCs on macrophage polarization.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Knee Osteoarthritis Progression in Mice through Polarization of M2 Macrophages by Intra-Articular Transplantation of Non-Cultured Human Adipose-Derived Regenerative Cells

Kamada

Matsushita

Yamashita

et al. 2021

JCM

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Adipose-derived regenerative cells (ADRCs) are non-cultured heterogeneous or mixed populations of cells obtained from adipose tissue by collagenase digestion. The injection of ADRCs have been tried clinically for the treatment of osteoarthritis (OA). The purpose of this study was to evaluate the effect of intra-articular transplantation of human ADRCs on OA progression in mice and the effect of ADRCs on macrophage polarization. In in vivo experiments, BALB/c-nu mice with knee OA received intra-articular transplantation of either phosphate buffered-saline or human ADRCs. OA progression was evaluated histologically and significantly attenuated in the ADRC group at both four and eight weeks postoperatively. The expression of OA-related proteins in the cartilage and macrophage-associated markers in the synovium were examined by immunohistochemistry. The numbers of MMP-13-, ADAMTS-5-, IL-1β-, IL-6- and iNOS-positive cells significantly decreased, and type II collagen- and CD206-positive cells were more frequently detected in the ADRC group compared with that in the control group. In vitro co-culture experiments showed that ADRCs induced macrophage polarization toward M2. The results of this study suggest that the intra-articular transplantation of human ADRCs could attenuate OA progression possibly by reducing catabolic factors in chondrocytes and modulating macrophage polarization.

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“…Stem cells, exosomes, and platelet-rich plasma (PRP) therapies can shift pro-inflammatory M1 into anti-inflammatory M2 macrophages by immunomodulatory bioactive factors through a series of complex mechanisms [48][49][50]. Our previous studies showed that CEFFE regulated inflammation by reducing the infiltration of macrophages in the skin [35].…”

Section: Discussionmentioning

confidence: 99%

Cell-Free Fat Extract Attenuate Osteoarthritis via Chondrocytes Regeneration and Macrophages Immunomodulation

Jia¹,

Kang²,

Cai³

et al. 2022

Preprint

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Background: The prevalence of osteoarthritis (OA) is increasing, yet clinically effective and economical treatments are unavailable. We have previously proposed a cell-free fat extract (CEFFE) containing multiple cytokines, which possessed anti-apoptotic, anti-oxidative, and proliferation promotion functions, as a “cell-free” strategy. In this study, we aimed to evaluate the therapeutic effect of CEFFE in vivo and in vitro . Methods: In vivo study, sodium iodoacetate-induced OA rats were treated with CEFFE by intra-articular injections for 8 weeks. Behavioral experiments were performed every two weeks. Histological analyses, anti-type II collagen, and toluidine staining provided structural evaluation. Macrophage infiltration was assessed by anti-CD68 and anti-CD206 staining. In vitro study, the effect of CEFFE on macrophage polarization and secretory factors was evaluated by flow cytometry, immunofluorescence, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of CEFFE on cartilage regeneration was accessed by cell counting kit-8 assay and qRT-PCR. The generation of reactive oxygen species (ROS) and levels of ROS-related enzymes were investigated by qRT-PCR and western blotting. Results: In rat models with sodium iodoacetate (MIA)-induced OA, CEFFE increased claw retraction pressure while decreasing bipedal pressure in a dose-depend manner. Moreover, CEFFE promoted cartilage structure restoration and increased the proportion of CD206 + macrophages in the synovium. In vitro , CEFFE decreased the proportion of CD86 + cells and reduced the expression of pro-inflammatory factors in LPS + IFN-γ induced Raw 264.7. In addition, CEFFE decreased the expression of interleukin-6 and ADAMTs-5 and promoted the expression of SOX-9 in mouse primary chondrocytes. Besides, CEFFE reduced the intracellular levels of reactive oxygen species in both in vitro models through regulating ROS-related enzymes. Conclusions: CEFFE inhibits the progression of OA by promoting cartilage regeneration and limiting low-grade joint inflammation.

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Effect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization

Cited by 64 publications

References 43 publications

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

Attenuation of Knee Osteoarthritis Progression in Mice through Polarization of M2 Macrophages by Intra-Articular Transplantation of Non-Cultured Human Adipose-Derived Regenerative Cells

Cell-Free Fat Extract Attenuate Osteoarthritis via Chondrocytes Regeneration and Macrophages Immunomodulation

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