(1) Background: There is increasing interest in the use of platelet-rich plasma and related orthobiologics for the treatment of chronic musculoskeletal disorders in horses; however, there is no information on the bibliometric impact of the literature published in this area. (2) Methods: A bibliometric analysis was performed using the bibliometrix R package by analyzing the documents registered in the WOS and Scopus databases from 2000 to 2024. The included registers were evaluated according to the menu of results from the biblioshiny web app (overview, sources, authors, documents, words, trending topics, clustering, conceptual structure, and social structure). (3) Conclusions: The documents produced were mainly published in Frontiers in Veterinary Science, Journal of Equine Veterinary Science, BMC Veterinary Research, and the American Journal of Veterinary Research). The most productive institutions were Universidad de Caldas, Colorado State University, University of California-Davis, and University of Leipzig, and the most productive countries were the USA, Brazil, and Colombia. Horse, platelet-rich plasma, equine, osteoarthritis, and autologous conditioned serum were the most frequently used keywords. The trending topics in this area are platelet lysates and orthobiologics. The collaboration network of authors, institutions, and countries shows an isolated development of individual author networks with modest collaboration between institutions and countries.

Platelet lysate (PL) is investigated as a potential replacement for fetal bovine serum (FBS) in cell culture. However, there is limited research on its impact on the immune profile of equine mesenchymal stromal cells (eMSCs). This study aimed to evaluate the effects of different PL formulations on the proliferative capacity, multipotentiality, and immune profile of equine adipose tissue-derived MSCs (eAD-MSCs). In vitro growth kinetics and trilineage differentiation of eAD-MSCs (n = 7) were assessed under three culture conditions: medium-concentration PL (MPL), high-concentration PL (HPL), and FBS as a control. The immune profile was evaluated by studying the expression of immunogenic receptors such as MHC I, MHC II, and immunomodulatory molecules IL-6, IL-10, and TNF-α, determined by gene expression, surface marker expression, and cytokine quantification. Both PL formulations, pooled from 5 donors, exhibited 3.3 and 6.5-fold higher platelet counts than baseline plasma for MPL and HPL, respectively. Higher concentrations of TGF-β and PDGF were found in both PL formulations compared to baseline. Furthermore, MPL and HPL subcultures demonstrated proliferative, clonogenic, and multipotent capacities similar to FBS. The immune profile of PL-cultured cells exhibited gene expression levels related to immunogenicity and immunomodulation similar to the reference condition, and the surface antigen presence of MHC II was also similar. However, HPL media exhibited higher IL-6, IL-10, and TNF-α concentrations in the culture supernatant. In conclusion, both PL media contained higher concentrations of growth factors compared to FBS, supporting the in vitro culture of eAD-MSCs with proliferative, clonogenic, and multipotent capacity similar to the reference medium. Nonetheless, PL usage led to a variation in the immunomodulatory cytokine microenvironment, with higher concentrations of IL-6, IL-10, and TNF-α in HPL media compared to MPL and FBS.

OBJECTIVE: To clarify the anti-inflammatory effect of platelet lysate (PL) on equine persistent synovitis by using a model of synovitis induced by monoiodoacetic acid (MIA).
METHODS: Nonseptic synovitis was induced by administering MIA into both antebrachiocarpal joints of 6 clinically healthy horses on day 0. On days 23, 30, and 37, carpal circumference measurement and synovial fluid collection for assays (leucocytes, LDH, tumor necrosis factor-α, and TGF-β1) were performed, after which PL was injected into 1 antebrachiocarpal joint and saline into the contralateral joint. Synovium and synovial fluid were obtained on day 44 for histological analysis and quantification of inflammation-related genes (matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs 4, receptor activator of nuclear factor κ-Β ligand, and collagen type I α2 chain) and the abovementioned proteins.
RESULTS: The LDH level on day 44 was significantly lower in the PL-injected joint than in the saline-treated one. However, no significant differences were found in the other indices quantified, including osteoclast counts on the synovium.
CONCLUSIONS: Multiple IA administration of PL does not exert anti-inflammatory effects on the equine persistent synovitis induced by MIA.
CONCLUSIONS: Intra-articular PL administration did not alter many inflammatory biomarkers, suggesting that PL does not have a direct anti-inflammatory effect. However, the reduction in synovial LDH levels suggests that PL promoted joint tissue repair and may consequently alleviate inflammation at the site of administration.

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Muscle-derived mesenchymal stromal cells (mdMSCs) hold great promise in regenerative medicine due to their immunomodulatory properties, multipotent differentiation capacity and ease of collection. However, traditional in vitro expansion methods use fetal bovine serum (FBS) and have numerous limitations including ethical concerns, batch-to-batch variability, immunogenicity, xenogenic contamination and regulatory compliance issues. This study investigates the use of 10% equine platelet lysate (ePL) obtained by plasmapheresis as a substitute for FBS in the culture of mdMSCs in innovative 2D and 3D models. Using muscle microbiopsies as the primary cell source in both models showed promising results. Initial investigations indicated that small variations in heparin concentration in 2D cultures strongly influenced medium coagulation with an optimal proliferation observed at final heparin concentrations of 1.44 IU/mL. The two novel models investigated showed that expansion of mdMSCs is achievable. At the end of expansion, the 3D model revealed a higher total number of cells harvested (64.60 ± 5.32 million) compared to the 2D culture (57.20 ± 7.66 million). Trilineage differentiation assays confirmed the multipotency (osteoblasts, chondroblasts and adipocytes) of the mdMSCs generated in both models with no significant difference observed. Immunophenotyping confirmed the expression of the mesenchymal stem cell (MSC) markers CD-90 and CD-44, with low expression of CD-45 and MHCII markers for mdMSCs derived from the two models. The generated mdMSCs also had great immunomodulatory properties. Specific immunological extraction followed by enzymatic detection (SIEFED) analysis demonstrated that mdMSCs from both models inhibited myeloperoxidase (MPO) activity in a strong dose-dependent manner. Moreover, they were also able to reduce reactive oxygen species (ROS) activity, with mdMSCs from the 3D model showing significantly higher dose-dependent inhibition compared to the 2D model. These results highlighted for the first time the feasibility and efficacy of using 10% ePL for mdMSC expansion in novel 2D and 3D approaches and also that mdMSCs have strong immunomodulatory properties that can be exploited to advance the field of regenerative medicine and cell therapy instead of using FBS with all its drawbacks.

Platelet lysate, derived from platelets, are valuable biological products rich in bioactive molecules. Their use promotes tissue healing and modulates inflammation. However, maintaining the stability and bioactivity of platelet lysate is challenging since they degrade rapidly at room temperature. This study focused on the possibility to confer enhanced stability to freeze-dried equine platelet lysate as an alternative to platelet-rich plasma (PRP). Platelet lysate (PL) was derived from PRP and freeze-dried either as such or using various adjuvants. Primary cell cultures of porcine Vascular Wall-Mesenchymal Stem Cells were treated with different PL formulations, and cell viability was assessed using an MTT assay. Overall, the addition of PL significantly improved cell viability as compared to controls without growth factor supplementation or with foetal bovine serum. Notably, the freeze-drying process maintained the effectiveness of the PL for at least a week. Furthermore, the study revealed that varying the horse as the source of PL could yield varying effects on cell viability. Detailed freeze-drying protocols were established, including freezing, primary drying and secondary drying phases, and the type of adjuvant. This study demonstrated the potential of freeze-dried equine PL as a viable alternative to PRP and highlighted the importance of precise freeze-drying protocols and adjuvants for standardization. Equine PL showed promise for medical treatment in horses, offering advantages such as extended shelf life, ease of handling, and reduced transportation costs, with the potential for broadened therapeutic usage.

Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL\'s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

UNASSIGNED: Platelet lysate is an acellular platelet product containing factors released from secretory granules, including cytokines and growth factors. This study aimed to evaluate different centrifugation methods used to prepare canine platelet lysate with variable content of leukocytes, plasma, and heat-sensitive proteins.
UNASSIGNED: Whole blood was collected from six dogs and two double-spin preparation methods were used to generate the platelet-rich plasma with reduced (PRP) and high (L-PRP) concentration of leukocytes. A portion of both methods underwent plasma depletion via centrifugation and platelet lysate was generated via freeze-thaw cycles. A portion of the generated platelet lysate underwent complement inactivation via heat treatment. Growth factors (TGF-β1, VEGF, TNF-α, PDGF-BB, HGF) were quantified in all different platelet lysate preparations using ELISAs.
UNASSIGNED: Both platelet-rich plasma preparations had a 6.7-fold increase in platelet concentration. White blood cell (WBC) concentration compared to whole blood increased 1.2-fold times in PRP and 1.9-fold times in L-PRP. Negligible concentrations of platelets, WBC, and hematocrit were identified in all lysate groups. Statistically significant differences were identified for PDGF, VEGF, and TNF-α, and not for TGF-β or HGF. No growth factor differences were noted between centrifugation methods. PDGF was significantly higher in platelet lysate that was plasma depleted. VEGF was significantly higher in heat-treated lysate groups. TNF-α concentrations were overall very low, though were noted to significantly increase following plasma depletion.
UNASSIGNED: These results support that growth factors and cytokine release can be affected by the platelet lysate preparation and processing.

UNASSIGNED: Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications.
UNASSIGNED: A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases.
UNASSIGNED: A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies.
UNASSIGNED: Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.

OBJECTIVE: Chondrocyte-based cell therapies are effective for the treatment of chondral lesions, but remain poorly indicated for diffuse lesions in the context of early osteoarthritis (OA). The aim of this study was to develop a protocol to obtain chondroprogenitor cells suitable for the treatment of diffuse chondral lesions within early OA.
METHODS: Cartilage cells were expanded at low density in human platelet lysate (hPL). A test was performed to exclude senescence. The expression of surface cluster of differentiation 146, cluster of differentiation 166, major histocompatibility complex (MHC)-I and MHC-II and of genes of interest were evaluated, as well as the trophic potential of these cells, by the assessment of lubricin and matrix production. The immunomodulatory potential was assessed through their co-culture with macrophages.
RESULTS: Cartilage cells expanded at low density in hPL showed higher proliferation rate than standard-density cells, no replicative senescence, low immunogenicity and expression of lubricin. Moreover, they presented an increased expression of chondrogenic and antihypertrophic markers, as well as a superior matrix deposition if compared to cells cultured at standard density. Cartilage cells induced on macrophages an upregulation of CD206, although a higher increase of CD163 expression was observed in the presence of low-density cells.
CONCLUSIONS: These findings lay the grounds to explore the clinical usefulness of low-density cultured cartilage cells to treat diffuse lesions in early OA joints for both autologous and allogenic use.
METHODS: Not applicable.