Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors

O'Shaughnessey, Krista; Matuska, Andrea M.; Hoeppner, Jacy; Farr, Jack; Klaassen, Mark A.; Kaeding, Christopher C.; Lattermann, Christian; King, William J.; Woodell-May, Jennifer

doi:10.1002/jor.22671

Cited by 54 publications

(93 citation statements)

References 35 publications

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“…In this study, APS was derived from control donors and tested on bovine cartilage explants which will not be the situation for patients being treated for OA. However, a recent study has demonstrated that APS from 105 OA patients contained high concentrations of anti‐inflammatory cytokines and growth factors similar to APS derived from healthy donors . Previous research has demonstrated that bovine and human cartilage explants similarly upregulate ECM degradation in a synergistic manner .…”

Section: Discussionmentioning

confidence: 92%

“…APS contains a statistically significant concentration increase of the following anabolic cytokines over baseline blood: EGF, IGF‐I, PDGF‐AB and ‐BB, VEGF, and TGF‐β1 . Furthermore, a recent study has measured elevated anabolic growth factor concentrations in the APS derived from 105 OA patients . The importance of synergistic growth factors on chondrocyte metabolism and subsequent cartilage growth has been previously demonstrated .…”

Section: Discussionmentioning

confidence: 99%

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Autologous solution protects bovine cartilage explants from IL‐1α‐ and TNFα‐induced cartilage degradation

Matuska

O'Shaughnessey

King

et al. 2013

Journal Orthopaedic Research

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Osteoarthritis (OA) is characterized by deterioration of articular cartilage driven by an imbalance of pro-and antiinflammatory cytokines. To address the cartilage deterioration observed in OA, an autologous protein solution (APS) has been developed which has been shown to inhibit the production of destructive proteases and inflammatory cytokines from chondrocytes and monocytes, respectively. The purpose of this study was to determine the chondroprotective effect of APS on IL-1a-or TNFa-challenged bovine articular cartilage explants. Cartilage explants were cultured in the presence or absence of recombinant inflammatory cytokines, IL-1a and TNFa. Explants under equivalent inflammatory conditions were pretreated with recombinant antagonists IL-1ra, sTNF-RI, or APS to measure their inhibition of matrix degradation. Explants were further evaluated with Safranin-O, Masson's Trichrome, and Hematoxylin and Eosin histological staining. APS was more effective than recombinant antagonists in preventing cartilage matrix degradation and inhibited any measurable IL-1a-induced collagen release over a 21-day culture period. APS treatment reduced the degree of Safranin-O staining loss when cartilage explants were cultured with IL-1a or TNFa. Micrographs of APS treated cartilage explants showed an increase in observed cellularity and apparent cell division. APS may have the potential to prevent cartilage loss associated with early OA. ß

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Autologous solution protects bovine cartilage explants from IL‐1α‐ and TNFα‐induced cartilage degradation

Matuska

O'Shaughnessey

King

et al. 2013

Journal Orthopaedic Research

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“…Another product of regenerative medicine and IL-1 receptor antagonist compound, autologous protein solution, has been described by O’Shaughnessey, et. al [20]. This was developed from the serum of patients with radiographic-proven osteoarthritis.…”

Section: Resultsmentioning

confidence: 99%

“…This was developed from the serum of patients with radiographic-proven osteoarthritis. Anti-inflammatory compounds isolated by immunosorbent assay in addition to IL-1 Ra include sIL-1RII, sTNF-RI, and sTNF-RII [20]. ,…”

Section: Resultsmentioning

confidence: 99%

Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine

Richards

Maxwell

Weng

et al. 2016

The Physician and Sportsmedicine

147

117

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Objectives Knee osteoarthritis (OA)1 is a debilitating condition that may ultimately require total knee arthroplasty (TKA)2. Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI)3. The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment. Methods A literature search was executed using Medline, Cochrane, and Embase with keywords ”knee osteoarthritis” and “injection.” Specifically, articles discussing intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP)4 and mesenchymal stem cells (MSC)5, were analyzed. Results Forty-five publications were scrutinized. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5. Papers included animal models. Local anesthetics have potential side effects and may only be effective for four hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to one months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation. Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint. Conclusions Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they may ultimately have profound implications in the way knee OA is managed.

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“…Attempts have been made to employ individual recombinant inhibitors of IL‐1β or TNFα as treatments for OA, but these anti‐cytokines have failed to prove effective in OA clinical trials . In contrast, an Autologous Protein Solution (APS) prepared from a patient's own blood contains concentrated anti‐inflammatory cytokines, including interleukin‐1 receptor antagonist (IL‐1ra) and soluble forms of the cell receptors for IL‐1 and TNFα (sIL‐1RII and sTNF‐R) . IL‐1ra blocks the signaling of IL‐1β, sIL‐1RII competitively binds with IL‐1β, and sTNF‐RII binds to TNFα .…”

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confidence: 99%

Human blood‐based anti‐inflammatory solution inhibits osteoarthritis progression in a meniscal‐tear rat study

King

Bendele

Marohl

et al. 2017

Journal Orthopaedic Research

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Current osteoarthritis (OA) research searches for treatments that modify the course of disease progression. Autologous Protein Solution (APS) is derived from whole blood and is a unique autologous therapy that contains high concentrations of white blood cells, platelets, and concentrated plasma, providing cytokines that can target the underlying mechanisms of disease progression. The APS Kit is currently under investigation for clinical use in the USA (NCT02262364). The aim of this study was to determine if APS has disease-modifying properties in the well-characterized rat meniscal tear-induced model of OA. Thirty male athymic rats underwent surgery to induce OA by a complete tear of the medial meniscus of the right knee. Seven days later, rats were administered 50 μl intra-articular (IA) APS from a human donor or phosphate buffered saline (PBS) control. Rats were euthanized 3 weeks following treatment and knee joints were processed for histological analysis. Collagen and cartilage degeneration were decreased by APS treatment, resulting in a significantly improved total joint score in APS-treated rats compared to those treated with the PBS control. No significant variations in gait analysis, weight gain, osteophyte score, or synovitis score were observed between APS- and PBS-treated animals. There were no adverse effects of APS reported in the study. Treatment with a single IA injection of APS reduced the cartilage degeneration that characterizes the progression of OA. Further studies are necessary to determine if APS can modify OA disease progression in humans. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2260-2268, 2017.

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Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors

Cited by 54 publications

References 35 publications

Autologous solution protects bovine cartilage explants from IL‐1α‐ and TNFα‐induced cartilage degradation

Autologous solution protects bovine cartilage explants from IL‐1α‐ and TNFα‐induced cartilage degradation

Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine

Human blood‐based anti‐inflammatory solution inhibits osteoarthritis progression in a meniscal‐tear rat study

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