Project description:IntroductionChemonucleolysis with condoliase (chondroitin sulfate ABC endolyase) has been used to treat patients with lumbar disc herniation (LDH) in Japan since 2018. In this study, we retrospectively investigated clinical outcomes in patients who received an intradiscal condoliase injection for LDH and sought to identify significant predictors of good outcome.MethodsIndications for treatment were as follows: (1) unilateral leg pain with or without back pain, (2) nerve root compression caused by LDH confirmed on magnetic resonance imaging (MRI), and (3) leg pain resistant to at least 1 month of conservative treatment, including medication, nerve root block, or physical therapy. Patients with motor weakness or a history of severe allergy were excluded, as were those with the foraminal or sequestrated type of LDH. The injection was defined as effective if the numeric rating scale score for leg pain improved by ≥50% at 6 months post-treatment.ResultsA total of 52 patients (mean age, 45.0 years) were enrolled and classified according to whether the injection was effective (E group, n=40, 76.9%) or less effective (L group, n=9, 17.3%). Three patients (5.8%) underwent herniotomy for residual pain within 6 months of the injection. There were no severe adverse events. Reduction of herniation was seen on MRI more often in the E group than in the L group. The effectiveness in patients with transligamentous LDH was similar to that in patients with subligamentous LDH. High-intensity signal change in the area of LDH on pretreatment T2-weighted MRI was a significant predictor of successful leg pain relief.ConclusionsAn intradiscal condoliase injection was a safe and effective treatment for painful radiculopathy caused by LDH. Leg pain was more likely to improve in patients with high-intensity signal change in the area of LDH before treatment.
Project description:BackgroundIntradiscal condoliase injection for lumbar disc herniation (LDH) was developed in Japan in 2018. The treatment is intermediate between conservative therapy and surgery, and its frequency is increasing. Condoliase is limited to a single application over a lifetime, rendering it important to understand the indications and predictors of its effectiveness. This review aimed to summarize published studies and provide appropriate indications and limitations for appropriate patient selection based on existing findings.MethodsWhile adhering to PRISMA guidelines, we searched the PubMed, Web of Science, and EMBASE databases to identify articles reporting the clinical outcomes of intradiscal condoliase injection for LDH. Data extraction focused on the effective rate, prognostic factors, and posttreatment imaging changes and was used in the meta-analysis.ResultsNineteen studies met the inclusion criteria. Our meta-analysis revealed 78% total response, 11% posttreatment surgery, and 42% posttreatment Pfirrmann-classification-grade progression rates. Posttreatment intervertebral disc degeneration was potentially associated with an improved response rate and disc regeneration one year posttreatment, especially in young patients. The Regimen for patients aged <20 and >70 years should be carefully selected, including those with a disease duration of >1 year, recurrent LDH, small-sized LDH, vertebral instability, and inadequate duration (<3 months) of conservative therapy.ConclusionsAlthough long-term outcomes and imaging changes must be evaluated owing to the heterogeneity of previous studies, intradiscal condoliase injection is a minimally invasive and cost-effective treatment option for patients with LDH. Treatment indications should be determined after carefully evaluating evidence from previous conservative and surgical treatments.
Project description:Study designSystematic review and meta-analysis.ObjectivesWe performed this meta-analysis to evaluate whether intradiscal Platelet Rich Plasma(PRP) injection has any beneficial role in the management of lumbar disc disease.MethodsWe conducted independent and duplicate electronic database searches including PubMed, Embase, and Cochrane Library till September 2020 for studies investigating the role of intradiscal PRP in the management of lumbar disc disease. The analysis was performed in the R platform using OpenMeta[Analyst] software.Results13 studies including 2 RCTs, 5 prospective, and 6 retrospective studies involving 319 patients were included in the meta-analysis. A single-arm meta-analysis of the included studies showed a beneficial effect of the intervention in terms of pain relief outcomes like VAS score (p < 0.001), pain component of SF-36 (p = 0.003) while such improvement was not seen in functional outcome measures like ODI score (p = 0.071), the physical component of SF-36 (p = 0.130) with significant heterogeneity noted among the included studies. No structural improvement in magnetic resonance imaging was observed (p = 0.106). No additional procedure-related adverse events were noted in the included studies (p = 0.662).ConclusionThere is a paucity of high-quality studies to give conclusive evidence on the benefits of intradiscal PRP for lumbar disc disease. Although intradiscal PRP injection has shown some beneficial effect in controlling pain for lumbar disc disease, we could not find structural or functional improvement from the included studies. Hence, we recommend large double-blind double-arm randomized controlled studies to analyze the benefits of the intervention being analyzed.
Project description:Study designIsolated human nucleus pulposus (hNP) cells from degenerated intervertebral disc were incubated under hydrostatic pressure and evaluated for regenerative potential.ObjectivesTo characterize metabolic turnover in hNP cells isolated from degenerated intervertebral discs classified by Pfirrmann grade under physiologically relevant hydrostatic pressure at high osmolality in vitro.Summary of background dataWe demonstrated that bovine caudal nucleus pulposus cells isolated from healthy cows produced more extracellular matrix under cyclic hydrostatic pressure followed by constant pressure (mimicking physiological intradiscal pressure in humans) than under no pressure in vitro. We assessed the effects of pressure on human degenerated cells isolated under the same regimen of pressure used for bovine cells.MethodshNP cells isolated from discarded tissue classified as Pfirrmann Grade 2-3 (n=13: age, 46.7±14.0) and Grade 4 (n=13: age, 53.0±11.5) were incubated under cyclic hydrostatic pressure at 0.2-0.7 MPa, 0.5 Hz for 2 days followed by constant pressure at 0.3 MPa for 1 day, repeated twice over 6 days. The gene expression and immunohistology of matrix molecules, catabolic and anti-catabolic proteins were evaluated.ResultsAggrecan and collagen type II expression was significantly more upregulated under HP in Grade 2-3 than in Grade 4 tissues (both, P<0.01). Linear regression analysis showed a positive correlation between matrix metalloproteinase 13 and tissue inhibitor for metalloproteinase 2 expression in Grade 2-3, while a negative correlation was found in Grade 4 (P<0.05). Immunohistological staining revealed the activation of a mechanoreceptor, transient receptor potential vanilloid 4, under HP.ConclusionsResident cells in mild-moderate degenerated disc classified as Pfirrmann grade 2-3 have the potential to promote extracellular matrix production and maintain adequate cell viability under physiological spinal loading.RelevanceThis study explored the potential of degenerated remnant NP cells under physiological environment, possibly leading to establishing strategies for IVD regeneration.
Project description:Mesenchymal stem cells (MSCs) have been optimal targets in the development of cell based therapies, but their limited availability and high death rate after transplantation remains a concern in clinical applications. This study describes novel effects of platelet rich clot releasate (PRCR) on rat bone marrow-derived MSCs (BM-MSCs), with the former driving a gene program, which can reduce apoptosis and promote the regenerative function of the latter in hostile microenvironments through enhancement of paracrine/autocrine factors. By using reverse transcription-polymerase chain reaction, immunofluorescence and western blot analyses, we showed that PRCR preconditioning could alleviate the apoptosis of BM-MSCs under stress conditions induced by hydrogen peroxide (H2O2) and serum deprivation by enhancing expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF) via stimulation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT/NF-?B signaling pathways. Furthermore, the effects of PRCR preconditioned GFP-BM-MSCs subcutaneously transplanted into rats 6?h after wound surgery were examined by histological and other tests from days 0-22 after transplantation. Engraftment of the PRCR preconditioned BM-MSCs not only significantly attenuated apoptosis and wound size but also improved epithelization and blood vessel regeneration of skin via regulation of the wound microenvironment. Thus, preconditioning with PRCR, which reprograms BM-MSCs to tolerate hostile microenvironments and enhance regenerative function by increasing levels of paracrine factors through PDGFR-?/PI3K/AKT/NF-?B signaling pathways would be a safe method for boosting the effectiveness of transplantation therapy in the clinic.
Project description:In this study, we aim to compare the therapeutic effects of PRP alone versus combination of PRP with primary glucocorticoid injection (GCI) at the early stage of tedinopathy. We hypothesize that PRP treatment could promote tendon regeneration through suppression of inflammation.
Project description:BackgroundPlatelet-rich plasma (PRP) has been shown to be a promising treatment for subacromial impingement, and although its interaction with aspirin (ASA) is controversial, many providers ask patients to stop non-steroidal anti-inflammatory drug use before PRP administration.PurposeThis studied aimed to identify the effect of PRP in a murine model of subacromial impingement and to explore the effect of ASA on PRP treatment.MethodsA murine model of subacromial impingement was used, incorporating 48 wild-type C57BL/6 mice. After impingement surgery, mice received either human PRP activated via calcium chloride or saline injected into the subacromial space. The mice received either drinking water with ASA or standard drinking water, creating 4 groups: saline injection, saline injection + ASA, PRP injection, and PRP injection + ASA. All injections occurred at 3 weeks after impingement surgery, and mice were evaluated at 6 weeks. Each mouse underwent gait analysis, biomechanical analysis (N = 10 shoulders), histological analysis (N = 6), and gene expression analysis (N = 8).ResultsBiomechanical testing showed increased load to failure in the PRP group compared to the ASA group, and increased stiffness in PRP vs saline, PRP vs ASA, and PRP vs ASA + PRP. Gene expression analysis identified 17 downregulated genes between the ASA + PRP and saline groups. Eight of these differentially expressed genes contribute to collagen biosynthesis and modification, 4 to extracellular matrix (ECM) synthesis, and 4 to ECM degradation.ConclusionsIn this preliminary analysis, PRP injections in a murine model of subacromial impingement demonstrated mixed effects on tendon quality and pain, and ASA did not have a consistent effect on the response to PRP.
Project description:BackgroundBecause the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs.MethodsRabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs.FindingsGene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs.InterpretationThese findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs.FundingMinistry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
Project description:Recent studies on cull cows have shown that ovarian abnormalities, particularly ovarian insufficiency, are the main cause of reproductive failure. The aim of this study was to treat bovine ovarian failure with intraovarian administration of autologous platelet rich plasma (PRP), which is rich in growth factors, chemokines, and cytokines that could stimulate follicular growth and steroidogenesis. Twelve cows with ovarian hypofunction were enrolled in the study and they were randomly allocated in control group (CTR) and treated group (six animal for group). In the treated group, only five animals received the PRP treatment because intraovarian administration was hindered in one by a rectovaginal fistula. Animals of control group were treated by intraovarian administration of physiological solution. In the 4 weeks after PRP injection, a mild to strong increase in progesterone (PRG) concentrations was detected in four of the five cows treated. Artificial insemination (AI) resulted in four pregnancies that are still ongoing (7th month). Intraovarian administration of PRP improved ovarian function after 2 months of treatment. This effect may be due to reduction of follicular atresia or to revitalization of dormant oocytes allowing restoration of fertility.
Project description:BackgroundStromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet rich plasma (PRP) can be obtained from peripheral blood. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF and PRP intra-discally into patients with degenerative disc disease.MethodsA total of 15 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the disc nucleus of patients with degenerative disc disease. The subjects were then monitored for adverse events, range of motion, visual analog scale (VAS), present pain intensity (PPI), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), Dallas Pain Questionnaire and Short Form (SF)-12 scores over a period of 6 months. Safety events were followed for 12 months.ResultsNo severe adverse events (SAEs) were reported during a 12 month follow up period with no incidences of infection. Patients demonstrated statistically significant improvements in several parameters including flexion, pain ratings, VAS, PPI, and short form questionnaires. In addition, both ODI and BDI data was trending positive and a majority of patients reported improvements in their Dallas Pain Questionnaire scores.ConclusionsOverall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy. Trial registration NCT02097862. Name of registry: www.clinicaltrials.gov . https://clinicaltrials.gov/ct2/show/NCT02097862?term=bioheart&rank=6 . Date of registration: March 25, 2014; Date of enrollment: March 2014.