Safety and Efficacy of Autologous Intra-articular Platelet Lysates in Early and Intermediate Knee Osteoarthrosis in Humans

Al-Ajlouni, Jihad; Awidi, Abdalla; Samara, Osama; Al-Najar, Mahasan; Tarwanah, Emad; Saleh, Mohannad Abou; Awidi, Mohammad; Hassan, Freh Abu; Samih, Mohammad; Bener, Abdulbari; Dweik, Manar

doi:10.1097/jsm.0000000000000166

Cited by 45 publications

(31 citation statements)

References 25 publications

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“…PRP was applied in clinical trials to treat cartilage disorders (Xie et al, ). A recent study also reported a beneficial effect of intra‐articular injection of PL (Al‐Ajlouni et al, ). Our observed beneficial activity of PL on the in vitro made cartilage provides a rationale to the application of PL on damaged cartilage.…”

Section: Discussionmentioning

confidence: 87%

Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1

Nguyen

Cancedda

Descalzi

2017

J Tissue Eng Regen Med

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The idea of rescuing the body self-repair capability lost during evolution is progressively gaining ground in regenerative medicine. In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. Aim of this study was to assess the potential of a platelet lysate (PL) for human articular cartilage repair considering its activity on progenitor cells and differentiated chondrocytes. PL induced the re-entry in the cell cycle of confluent, growth-arrested dedifferentiated/progenitor cartilage cells. In a cartilage permissive culture environment, differentiated cells also resumed proliferation after exposure to PL. These findings correlated with an up-regulation of the proliferation/survival pathways ERKs and Akt and with an induction of cyclin D1. In short- and long-term cultures of articular cartilage explants, we observed a release of proliferating chondroprogenitors able to differentiate and form an "in vitro" tissue with properties of healthy articular cartilage. Moreover, in cultured cartilage cells, PL induced a hypoxia-inducible factor (HIF-1) alpha increase, its nuclear relocation and the binding to HIF-1 responsive elements. These events were possibly related to the cell proliferation because the HIF-1 inhibitor acriflavine inhibited HIF-1 binding to HIF-1 responsive elements and cell proliferation. Our study demonstrates that PL induces quiescent cartilage cell activation and proliferation leading to new cartilage formation, identifies PL activated pathways playing a role in these processes, and provides a rationale to the application of PL for therapeutic treatment of damaged articular cartilage.

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Section: Discussionmentioning

confidence: 87%

Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1

Nguyen

Cancedda

Descalzi

2017

J Tissue Eng Regen Med

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“…There has been increasing interest in the use of platelet lysate (PL) instead of PRP as PL is an acellular preparation containing high concentrations of growth factors and cytokines ( 31 – 48 ). The acellular nature of PL is important because it has the potential to be used in an allogeneic manner with further processing to remove immunoglobulins and also because it can be quality tested and then stored frozen to have available for immediate patient use ( 31 – 48 ). Furthermore, the use of pooled PL, or PL generated from multiple healthy donors, is being explored to capitalize on the natural variability that exists between individuals and the growth factors and cytokines that are released from their platelets upon lysis.…”

Section: Introductionmentioning

confidence: 99%

Pooled Platelet-Rich Plasma Lysate Therapy Increases Synoviocyte Proliferation and Hyaluronic Acid Production While Protecting Chondrocytes From Synoviocyte-Derived Inflammatory Mediators

et al. 2018

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Platelet-rich plasma (PRP) preparations are being used with moderate success to treat osteoarthritis (OA) in humans and in veterinary species. Such preparations are hindered, however, by being autologous in nature and subject to tremendous patient and processing variability. For this reason, there has been increasing interest in the use of platelet lysate preparations instead of traditional PRP. Platelet lysate preparations are acellular, thereby reducing concerns over immunogenicity, and contain high concentrations of growth factors and cytokines. In addition, platelet lysate preparations can be stored frozen for readily available use. The purpose of this study was to evaluate the effects of a pooled allogeneic platelet-rich plasma lysate (PRP-L) preparation on equine synoviocytes and chondrocytes challenged with inflammatory mediators in-vitro to mimic the OA joint environment. Our hypothesis was that PRP-L treatment of inflamed synoviocytes would protect chondrocytes challenged with synoviocyte conditioned media by reducing synoviocyte pro-inflammatory cytokine production while increasing synoviocyte anti-inflammatory cytokine production. Synoviocytes were stimulated with either interleukin-1β (IL-1β) or lipopolysaccharide (LPS) for 24 h followed by no treatment or treatment with platelet-poor plasma lysate (PPP-L) or PRP-L for 48 h. Synoviocyte growth was evaluated at the end of the treatment period and synoviocyte conditioned media was assessed for concentrations of hyaluronic acid (HA), IL-1β, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Chondrocytes were then challenged for 48 h with synoviocyte conditioned media from each stimulation and treatment group and examined for gene expression of collagen types I (COL1A1), II (COL2A1), and III (COL3A1), aggrecan (ACAN), lubricin (PRG4), and matrix metallopeptidase 3 (MMP-3) and 13 (MMP-13). Treatment of inflamed synoviocytes with PRP-L resulted in increased synoviocyte growth and increased synoviocyte HA and IL-6 production. Challenge of chondrocytes with conditioned media from PRP-L treated synoviocytes resulted in increased collagen type II and aggrecan gene expression as well as decreased MMP-13 gene expression. The results of this study support continued investigation into the use of pooled PRP-L for the treatment of osteoarthritis and warrant further in-vitro studies to discern the mechanisms of action of PRP-L.

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“…Platelet Lysate (PL) is a biological platelet derivative rich in growth factors and cytokines that encourage tissue repair, which is driven by a multitude of growth factors including basic fibroblast-derived growth factor (bFGF), transforming growth factor beta (TGF-), platelet derived growth factor-AA (PDGF-AA), PDGF-AB, PDGF-BB, [19,20]. Increasingly, PL is being injected directly into OA knee joints with some encouraging results [21] but the mechanisms of its action remain unknown. In 2005, Doucet proposed the use of PL as a substitute to FCS for MSC expansion intended for cellular therapy [22].…”

Section: Introductionmentioning

confidence: 99%

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use

et al. 2018

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Safety and Efficacy of Autologous Intra-articular Platelet Lysates in Early and Intermediate Knee Osteoarthrosis in Humans

Cited by 45 publications

References 25 publications

Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1

Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1

Pooled Platelet-Rich Plasma Lysate Therapy Increases Synoviocyte Proliferation and Hyaluronic Acid Production While Protecting Chondrocytes From Synoviocyte-Derived Inflammatory Mediators

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use

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