المؤلفون: Tamagawa, Shota^1,2 (AUTHOR) s-tamagawa@juntendo.ac.jp, Sakai, Daisuke^2,3 (AUTHOR) daisakai@is.icc.u-tokai.ac.jp, Nojiri, Hidetoshi¹ (AUTHOR) hnojiri@juntendo.ac.jp, Sato, Masato^2,3 (AUTHOR), Ishijima, Muneaki¹ (AUTHOR) mi@juntendo.ac.jp, Watanabe, Masahiko^2,3 (AUTHOR)

المصدر: Diagnostics (2075-4418). Mar2022, Vol. 12 Issue 3, p707-707. 16p.

مصطلحات موضوعية: *INTERVERTEBRAL disk, *FUNCTIONAL magnetic resonance imaging, *MAGNETIC resonance imaging, *SOCIAL degeneration, *LUMBAR pain

مستخلص: 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. [ABSTRACT FROM AUTHOR]

المؤلفون: Schol, Jordy^1,2 (AUTHOR), Ambrosio, Luca^1,3,4 (AUTHOR), Tamagawa, Shota^1,5 (AUTHOR), Joyce, Kieran^6,7 (AUTHOR), Ruiz-Fernández, Clara^1,2 (AUTHOR), Nomura, Akira¹ (AUTHOR), Sakai, Daisuke^1,2 (AUTHOR) daisakai@is.icc.u-tokai.ac.jp

المصدر: Scientific Reports. 6/4/2024, Vol. 14 Issue 1, p1-16. 16p.

مصطلحات موضوعية: *HERNIA, *LACTATE dehydrogenase, *WEB databases, *PAIN measurement, *SCIENCE databases

مستخلص: Lumbar disc herniation (LDH) is often managed surgically. Enzymatic chemonucleolysis emerged as a non-surgical alternative. This systematic review and meta-analysis aims to assess the efficacy and safety of chemonucleolytic enzymes for LDH. The primary objective is to evaluate efficacy through "treatment success" (i.e., pain reduction) and severe adverse events (SAEs) rates. Additionally, differences in efficacy and safety trends among chemonucleolytic enzymes are explored. Following our PROSPERO registered protocol (CRD42023451546) and PRISMA guidelines, a systematic search of PubMed and Web of Science databases was conducted up to July 18, 2023. Inclusion criteria involved human LDH treatment with enzymatic chemonucleolysis reagents, assessing pain alleviation, imaging changes, and reporting on SAEs, with focus on allergic reactions. Quality assessment employed the Cochrane Source of Bias and MINORS tools. Meta-analysis utilized odds ratios (OR) with 95% confidence intervals (CI). Among 62 included studies (12,368 patients), chemonucleolysis demonstrated an 79% treatment success rate and significantly outperformed placebo controls (OR 3.35, 95% CI 2.41–4.65) and scored similar to surgical interventions (OR 0.65, 95% CI 0.20–2.10). SAEs occurred in 1.4% of cases, with slightly higher rates in chymopapain cohorts. No significant differences in "proceeding to surgery" rates were observed between chemonucleolysis and control cohorts. Limitations include dated and heterogeneous studies, emphasizing the need for higher-quality trials. Further optimization through careful patient selection and advances in therapy implementation may further enhance outcomes. The observed benefits call for wider clinical exploration and adoption. No funding was received for this review. [ABSTRACT FROM AUTHOR]

المؤلفون: Ambrosio, Luca^1,2,3 (AUTHOR), Schol, Jordy³ (AUTHOR), Ruiz-Fernandez, Clara^3,4 (AUTHOR), Tamagawa, Shota^3,5 (AUTHOR), Soma, Hazuki³ (AUTHOR), Tilotta, Veronica² (AUTHOR), Di Giacomo, Giuseppina² (AUTHOR), Cicione, Claudia² (AUTHOR), Nakayama, Shunya⁶ (AUTHOR), Kamiya, Kosuke⁶ (AUTHOR), Papalia, Rocco^1,2 (AUTHOR), Sato, Masato³ (AUTHOR), Vadalà, Gianluca^1,2 (AUTHOR), Watanabe, Masahiko³ (AUTHOR), Denaro, Vincenzo¹ (AUTHOR), Sakai, Daisuke³ (AUTHOR) daisakai@is.icc.u-tokai.ac.jp

المصدر: European Spine Journal. May2024, Vol. 33 Issue 5, p1713-1727. 15p.

مصطلحات موضوعية: *NUCLEUS pulposus, *EXTRACELLULAR vesicles, *INTERVERTEBRAL disk, *LABORATORY rats, *CELLULAR aging, *CELL communication, *IMMUNOSENESCENCE, *LEG pain

مستخلص: Purpose: To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. Methods: EVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1β. Thereafter, 16 Sprague–Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. Results: NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. Conclusion: Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics. [ABSTRACT FROM AUTHOR]

المؤلفون: Soma, Hazuki^1,2 (AUTHOR) soma.hazuki@tunzpharma.co.jp, Sakai, Daisuke^1,3 (AUTHOR) daisakai@is.icc.u-tokai.ac.jp, Nakamura, Yoshihiko¹ (AUTHOR) takayuki.warita@tunzpharma.co.jp, Tamagawa, Shota⁴ (AUTHOR) s-tamagawa@juntendo.ac.jp, Warita, Takayuki^1,2 (AUTHOR) schol.jordy@gmail.com, Schol, Jordy^1,3 (AUTHOR) me091130@tsc.u-tokai.ac.jp, Matsushita, Erika¹ (AUTHOR) sato-m@is.icc.u-tokai.ac.jp, Naiki, Mitsuru² (AUTHOR), Sato, Masato^1,3 (AUTHOR) masahiko@is.icc.u-tokai.ac.jp, Watanabe, Masahiko^1,3 (AUTHOR)

المصدر: International Journal of Molecular Sciences. Dec2023, Vol. 24 Issue 23, p16713. 16p.

مصطلحات موضوعية: *NUCLEUS pulposus, *PROGENITOR cells, *INTERVERTEBRAL disk, *EXTRACELLULAR matrix, *INDUSTRIAL capacity

مستخلص: The angiopoietin-1 receptor (Tie2) marks specific nucleus pulposus (NP) progenitor cells, shows a rapid decline during aging and intervertebral disc degeneration, and has thus sparked interest in its utilization as a regenerative agent against disc degeneration. However, the challenge of maintaining and expanding these progenitor cells in vitro has been a significant hurdle. In this study, we investigated the potential of laminin-511 to sustain Tie2+ NP progenitor cells in vitro. We isolated cells from human NP tissue (n = 5) and cultured them for 6 days on either standard (Non-coat) or iMatrix-511 (laminin-511 product)-coated (Lami-coat) dishes. We assessed these cells for their proliferative capacity, activation of Erk1/2 and Akt pathways, as well as the expression of cell surface markers such as Tie2, GD2, and CD24. To gauge their regenerative potential, we examined their extracellular matrix (ECM) production capacity (intracellular type II collagen (Col2) and proteoglycans (PG)) and their ability to form spherical colonies within methylcellulose hydrogels. Lami-coat significantly enhanced cell proliferation rates and increased Tie2 expression, resulting in a 7.9-fold increase in Tie2-expressing cell yields. Moreover, the overall proportion of cells positive for Tie2 also increased 2.7-fold. Notably, the Col2 positivity rate was significantly higher on laminin-coated plates (Non-coat: 10.24% (±1.7%) versus Lami-coat: 26.2% (±7.5%), p = 0.010), and the ability to form spherical colonies also showed a significant improvement (Non-coat: 40.7 (±8.8)/1000 cells versus Lami-coat: 70.53 (±18.0)/1000 cells, p = 0.016). These findings demonstrate that Lami-coat enhances the potential of NP cells, as indicated by improved colony formation and proliferative characteristics. This highlights the potential of laminin-coating in maintaining the NP progenitor cell phenotype in culture, thereby supporting their translation into prospective clinical cell-transplantation products. [ABSTRACT FROM AUTHOR]

المؤلفون: Munesada, Daiki¹ (AUTHOR) munesada.daiki.k@tokai.ac.jp, Sakai, Daisuke^1,2 (AUTHOR) daisakai@is.icc.u-tokai.ac.jp, Nakamura, Yoshihiko³ (AUTHOR) kahiko@is.icc.u-tokai.ac.jp, Schol, Jordy^1,2,3 (AUTHOR) me091130@tsc.u-tokai.ac.jp, Matsushita, Erika³ (AUTHOR), Tamagawa, Shota^1,4 (AUTHOR) k.sako0626@gmail.com, Sako, Kosuke¹ (AUTHOR) ogswr.a.817@gmail.com, Ogasawara, Shota¹ (AUTHOR) sato-m@is.icc.u-tokai.ac.jp, Sato, Masato^1,2 (AUTHOR) masahiko@is.icc.u-tokai.ac.jp, Watanabe, Masahiko^1,2 (AUTHOR)

المصدر: International Journal of Molecular Sciences. Aug2023, Vol. 24 Issue 15, p12289. 13p.

مصطلحات موضوعية: *NUCLEUS pulposus, *HYALURONIC acid, *INTERVERTEBRAL disk, *REACTIVE oxygen species, *PROGENITOR cells, *DIMETHYL sulfoxide, *CRYOPROTECTIVE agents

مستخلص: To develop an off-the-shelf therapeutic product for intervertebral disc (IVD) repair using nucleus pulposus cells (NPCs), it is beneficial to mitigate dimethyl sulfoxide (DMSO)-induced cytotoxicity caused by intracellular reactive oxygen species (ROS). Hyaluronic acid (HA) has been shown to protect chondrocytes against ROS. Therefore, we examined the potential of HA on mitigating DMSO-induced cytotoxicity for the enhancement of NPC therapy. Human NPC cryopreserved in DMSO solutions were thawed, mixed with equal amounts of EDTA-PBS (Group E) or HA (Group H), and incubated for 3–5 h. After incubation, DMSO was removed, and the cells were cultured for 5 days. Thereafter, we examined cell viability, cell proliferation rates, Tie2 positivity (a marker of NP progenitor cells), and the estimated numbers of Tie2 positive cells. Fluorescence intensity of DHE and MitoSOX staining, as indicators for oxidative stress, were evaluated by flow cytometry. Group H showed higher rates of cell proliferation and Tie2 expressing cells with a trend toward suppression of oxidative stress compared to Group E. Thus, HA treatment appears to suppress ROS induced by DMSO. These results highlight the ability of HA to maintain NPC functionalities, suggesting that mixing HA at the time of transplantation may be useful in the development of off-the-shelf NPC products. [ABSTRACT FROM AUTHOR]

المؤلفون: Sato, Tatsuya¹ (AUTHOR), Nojiri, Hidetoshi¹ (AUTHOR) hnojiri@juntendo.ac.jp, Okuda, Takatoshi¹ (AUTHOR), Miyagawa, Kei¹ (AUTHOR), Kobayashi, Nozomu¹ (AUTHOR), Takahashi, Ryosuke¹ (AUTHOR), Shimura, Arihisa¹ (AUTHOR), Tamagawa, Shota¹ (AUTHOR), Ohara, Yukoh² (AUTHOR), Hara, Takeshi² (AUTHOR), Ishijima, Muneaki¹ (AUTHOR)

المصدر: BMC Musculoskeletal Disorders. 9/7/2022, Vol. 23 Issue 1, p1-11. 11p.

مصطلحات موضوعية: *ADOLESCENT idiopathic scoliosis, *COMPACT bone, *MULTIPLE regression analysis, *VERTEBRAE, *COMPUTED tomography, *LATERAL dominance

مستخلص: Background: This study aimed to investigate the laterality of the pedicle morphology at the apical vertebra (AV) level and identify the radiographic factors associated with the laterality ratio of the pedicle morphology at the AV level in patients with adolescent idiopathic scoliosis (AIS).Methods: Overall, 684 pedicles in 57 AIS patients aged 10-20 years, who underwent preoperative computed tomography (CT) and had Lenke type 1 or 2 with right convex main thoracic curves (MTC), were evaluated. Pedicle diameters of the MTC were assessed. We defined and compared the region containing two vertebrae adjacent to the AV (APEX±1) and the region containing two vertebrae adjacent to the neutral vertebra. We analyzed the pedicle diameter and laterality ratio of APEX±1 and performed multiple linear regression analysis to identify the radiographic factors associated with the laterality of the pedicle diameter.Results: On the concave side of APEX±1, the pedicles of 15 patients (26.3%) did not accept a 4-mm-diameter pedicle screw (PS), even with 25% cortical bone width expansion. Laterality ratio differences in the pedicle diameters of the cortical bone width in APEX±1 were large in patients with more proximal AV level (p < 0.001) and smaller apical vertebral rotation (AVR) (p = 0.029).Conclusions: Preoperative planning to accurately select and insert the PS in AIS should be based on the anatomical limitations in APEX±1, AV level, and AVR degree. In APEX±1, the correlation between AVR and the laterality ratio of the pedicle diameter may be useful for pathoetiological interpretation of the AIS deformity. [ABSTRACT FROM AUTHOR]