Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.

Low back pain is critical health, social, and economic issue in modern societies. This disease is often associated with intervertebral disc degeneration; however, contemporary treatments are unable to target this underlying pathology to alleviate the pain symptoms. Cell therapy offers a promising novel therapeutic that, in theory, should be able to reduce low back pain through mitigating the degenerative disc environment. With the clinical development of cell therapeutics ongoing, this review aims to summarize reporting on the different clinical trials and assess the different regenerative strategies being undertaken to collectively obtain an impression on the potential safety and effectiveness of cell therapeutics against intervertebral disc-related diseases.

In recent years, various quantitative and functional magnetic resonance imaging (MRI) sequences have been developed and used in clinical practice for the diagnosis of patients with low back pain (LBP). Until now, T2-weighted imaging (T2WI), a visual qualitative evaluation method, has been used to diagnose intervertebral disc (IVD) degeneration. However, this method has limitations in terms of reproducibility and inter-observer agreement. Moreover, T2WI observations do not directly relate with LBP. Therefore, new sequences such as T2 mapping, T1ρ mapping, and MR spectroscopy have been developed as alternative quantitative evaluation methods. These new quantitative MRIs can evaluate the anatomical and physiological changes of IVD degeneration in more detail than conventional T2WI. However, the values obtained from these quantitative MRIs still do not directly correlate with LBP, and there is a need for more widespread use of techniques that are more specific to clinical symptoms such as pain. In this paper, we review the state-of-the-art methodologies and future challenges of quantitative MRI as an imaging diagnostic tool for IVD degeneration and painful discs.

Previous work showed a link between Tie2+ nucleus pulposus progenitor cells (NPPC) and disc degeneration. However, NPPC remain difficult to maintain in culture. Here, we report whole tissue culture (WTC) combined with fibroblast growth factor 2 (FGF2) and chimeric FGF (cFGF) supplementation to support and enhance NPPC and Tie2 expression. We also examined the role of PI3K/Akt and MEK/ERK pathways in FGF2 and cFGF-induced Tie2 expression. Young herniating nucleus pulposus tissue was used. We compared WTC and standard primary cell culture, with or without 10 ng/mL FGF2. PI3K/Akt and MEK/ERK signaling pathways were examined through western blotting. Using WTC and primary cell culture, Tie2 positivity rates were 7.0 ± 2.6% and 1.9 ± 0.3% (p = 0.004), respectively. Addition of FGF2 in WTC increased Tie2 positivity rates to 14.2 ± 5.4% (p = 0.01). FGF2-stimulated expression of Tie2 was reduced 3-fold with the addition of the MEK inhibitor PD98059 (p = 0.01). However, the addition of 1 μM Akt inhibitor, 124015-1MGCN, only reduced small Tie2 expression (p = 0.42). cFGF similarly increased the Tie2 expression, but did not result in significant phosphorylation in both the MEK/ERK and PI3K/Akt pathways. WTC with FGF2 addition significantly increased Tie2 maintenance of human NPPC. Moreover, FGF2 supports Tie2 expression via MEK/ERK and PI3K/Akt signals. These findings offer promising tools and insights for the development of NPPC-based therapeutics.

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.

We investigated the incidence and clinical features of cage subsidence after single-level lateral lumbar interbody fusion (LLIF). We studied a retrospective cohort of 59 patients (34 males, 25 females; mean age, 68.9 years) who received single-level LLIF. Patients were classified into subsidence and no-subsidence groups. Cage subsidence was defined as any violation of either endplate, classified using radiographs and computed tomography (CT) images. After one year, we compared patient characteristics, surgical parameters, radiological findings, pain scores, and fusion status. We also compared the Hounsfield unit (HU) endplate value obtained on CT preoperatively. Twenty patients (33.9%) had radiographic evidence of interbody cage subsidence. There were significant differences between the subsidence and no-subsidence groups in sex, cage height, fusion rate, and average HU value of both endplates (p < 0.05). There were no significant differences in age, height, weight, or body mass index. Moreover, there were no significant differences in global alignment and Numerical Rating Scale change in low back pain, leg pain, and numbness. Despite suggestions that patients with lower HU values might develop cage subsidence, our results showed that cage subsidence after single-level LLIF was not associated with low back pain, leg pain, or numbness one year post-operation.

Osteoarthritis (OA) of the knee is a disease that significantly decreases the quality of life due to joint deformation and pain caused by degeneration of articular cartilage. Since the degeneration of cartilage is irreversible, intervention from an early stage and control throughout life is important for OA treatment. For the treatment of early OA, the development of a disease-modifying osteoarthritis drug (DMOAD) for intra-articular (IA) injection, which is attracting attention as a point-of-care therapy, is desired. In recent years, the molecular mechanisms involved in OA progression have been clarified while new types of drug development methods based on gene sequences have been established. In addition to conventional chemical compounds and protein therapeutics, the development of DMOAD from the new modalities such as gene therapy and oligonucleotide therapeutics is accelerating. In this review, we have summarized the current status and challenges of DMOAD for IA injection, especially for protein therapeutics, gene therapy, and oligonucleotide therapeutics.

Background: Multiple studies have examined the potential of growth factors (GF) to enable mesenchymal stromal cells (MSC) to nucleus pulposus (NP) cell-like cell differentiation. Here we screened a wide range of GF and GF combinations for supporting NP cell-like cell differentiation. Methods: Human MSC were stimulated using 86 different GF combinations of TGF-β1, -2, -3, GDF5, -6, Wnt3a, -5a, -11, and Shh. Differentiation potency was assessed by alcian blue assay and NP cell marker expression (e.g., COL2A1, CD24, etc.). The top four combinations and GDF5/TGF-β1 were further analyzed in 3D pellet cultures, on their ability to similarly induce NP cell differentiation. Results: Almost all 86 GF combinations showed their ability to enhance proteoglycan production in alcian blue assay. Subsequent qPCR analysis revealed TGF-β2/Wnt3a, TGF-β1/Wnt3a, TGF-β1/Wnt3a/GDF6, and Wnt3a/GDF6 as the most potent combinations. Although in pellet cultures, these combinations supported NP marker expression, none showed the ability to significantly induce chondrogenic NP matrix production. Only GDF5/TGF-β1 resulted in chondrogenic pellets with significantly enhanced glycosaminoglycan content. Conclusion: GDF5/TGF-β1 was suggested as an optimal GF combination for MSC to NP cell induction, although further assessment using a 3D and in vivo environment is required. Wnt3a proved promising for monolayer-based NP cell differentiation, although further validation is required.