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Can intra-articular injection of freeze-dried platelet-derived factor concentrate regenerate articular cartilage in the knee joint?

ABSTRACT: Freeze-drying methods not only enable the delivery of growth factors using platelets, but also extend the shelf-life of platelet concentrates. The present study shows the clinical results of treating knee osteoarthritis with freeze-dried platelet-derived factor concentrate (PFC). While it improved pain, activities of daily living, sports and recreational activities, and knee-related quality of life, it did not significantly improve symptoms other than pain, such as restricted range of motion and mechanical symptoms. As such, the treatment effect may be attributed to anti-inflammatory action rather than actual cartilage regeneration.

SUBMITTER: Shirata T

PROVIDER: S-EPMC6517792 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Can intra-articular injection of freeze-dried platelet-derived factor concentrate regenerate articular cartilage in the knee joint?

Shirata Tomohiko T Kato Yuki Y

Regenerative therapy 20190510

Freeze-drying methods not only enable the delivery of growth factors using platelets, but also extend the shelf-life of platelet concentrates. The present study shows the clinical results of treating knee osteoarthritis with freeze-dried platelet-derived factor concentrate (PFC). While it improved pain, activities of daily living, sports and recreational activities, and knee-related quality of life, it did not significantly improve symptoms other than pain, such as restricted range of motion and ...[more]

PMID: 31193113

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Project description:Most forms of arthritis are incurable, difficult to treat, and a major cause of disability in Western countries. Better local treatment of arthritis is impaired by the pharmacokinetics of the joint that make it very difficult to deliver drugs to joints at sustained, therapeutic concentrations. This is especially true of biologic drugs, such as proteins and RNA, many of which show great promise in preclinical studies. Gene transfer provides a strategy for overcoming this limitation. The basic concept is to deliver cDNAs encoding therapeutic products by direct intra-articular injection, leading to sustained, endogenous synthesis of the gene products within the joint. Proof of concept has been achieved for both in vivo and ex vivo gene delivery using a variety of vectors, genes, and cells in several different animal models. There have been a small number of clinical trials for rheumatoid arthritis (RA) and osteoarthritis (OA) using retrovirus vectors for ex vivo gene delivery and adeno-associated virus (AAV) for in vivo delivery. AAV is of particular interest because, unlike other viral vectors, it is able to penetrate deep within articular cartilage and transduce chondrocytes in situ. This property is of particular importance in OA, where changes in chondrocyte metabolism are thought to be fundamental to the pathophysiology of the disease. Authorities in Korea have recently approved the world's first arthritis gene therapy. This targets OA by the injection of allogeneic chondrocytes that have been transduced with a retrovirus carrying transforming growth factor-?1 cDNA. Phase III studies are scheduled to start in the United States soon. Meanwhile, two additional Phase I trials are listed on Clinicaltrials.gov , both using AAV. One targets RA by transferring interferon-?, and the other targets OA by transferring interleukin-1 receptor antagonist. The field is thus gaining momentum and promises to improve the treatment of these common and debilitating diseases.

Project description:Tissue material properties are crucial to understanding their mechanical function, both in healthy and diseased states. However, in certain circumstances logistical limitations can prevent testing on fresh samples necessitating one or more freeze-thaw cycles. To date, the nature and extent to which the material properties of articular cartilage are altered by repetitive freezing have not been explored. Therefore, the aim of this study is to quantify how articular cartilage mechanical properties, measured by nanoindentation, are affected by multiple freeze-thaw cycles. Canine cartilage plugs (n = 11) from medial and lateral femoral condyles were submerged in phosphate buffered saline, stored at 3-5°C and tested using nanoindentation within 12h. Samples were then frozen at -20°C and later thawed at 3-5°C for 3h before material properties were re-tested and samples re-frozen under the same conditions. This process was repeated for all 11 samples over three freeze-thaw cycles. Overall mean and standard deviation of shear storage modulus decreased from 1.76 ± 0.78 to 1.21 ± 0.77MPa (p = 0.91), shear loss modulus from 0.42 ± 0.19 to 0.39 ± 0.17MPa (p=0.70) and elastic modulus from 5.13 ± 2.28 to 3.52 ± 2.24MPa (p = 0.20) between fresh and three freeze-thaw cycles respectively. The loss factor increased from 0.31 ± 0.38 to 0.71 ± 1.40 (p = 0.18) between fresh and three freeze-thaw cycles. Inter-sample variability spanned as much as 10.47MPa across freezing cycles and this high-level of biological variability across samples likely explains why overall mean "whole-joint" trends do not reach statistical significance across the storage conditions tested. As a result multiple freeze-thaw cycles cannot be explicitly or statistically linked to mechanical changes within the cartilage. However, the changes in material properties observed herein may be sufficient in magnitude to impact on a variety of clinical and scientific studies of cartilage, and should be considered when planning experimental protocols.

Dataset Information

Can intra-articular injection of freeze-dried platelet-derived factor concentrate regenerate articular cartilage in the knee joint?

Publications

Can intra-articular injection of freeze-dried platelet-derived factor concentrate regenerate articular cartilage in the knee joint?

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