Dataset Information

Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies.

ABSTRACT: BACKGROUND:Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult. PURPOSE:To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies. STUDY DESIGN:Systematic review. METHODS:A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based. RESULTS:After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold implantation or injection of a scaffold alone. None of the studies mentioned in this review compare the effectiveness of different (cell-seeded) scaffolds. CONCLUSION:There is heterogeneity in animal models, cell types, and scaffolds used, and limited comparative studies are available. The comparative in vivo research that is currently available is insufficient to draw strong conclusions as to which cell type is the most promising. However, there is a vast amount of in vivo research on the use of different types of multipotent mesenchymal stromal (stem) cells in different experimental settings, and good results are reported in terms of tissue formation. None of these studies compare the effectiveness of different cell-scaffold combinations, making it hard to conclude which scaffold has the greatest potential.

SUBMITTER: Korpershoek JV

PROVIDER: S-EPMC5347439 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies.

Korpershoek Jasmijn V JV de Windt Tommy S TS Hagmeijer Michella H MH Vonk Lucienne A LA Saris Daniel B F DB

Orthopaedic journal of sports medicine 20170221 2

<h4>Background</h4>Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, ...[more]

PMID: 28321424

Similar Datasets

Project description:Injury to the meniscus is common, but few viable strategies exist for its repair or regeneration. To address this, animal models have been developed to translate new treatment strategies toward the clinic. However, there is not yet a regulatory document guiding such studies. The purpose of this study was to carry out a systematic review of the literature on meniscus treatment methods and outcomes to define the state of the field. Public databases were queried by using search terms related to animal models and meniscus injury and/or repair over the years 1980-2015. Identified peer-reviewed manuscripts were screened by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. One of nine reviewers read each manuscript and scored them based on whether the publication described a series of predefined study descriptors and outcome measures. Additional data were extracted to identify common assays used. A total of 128 full-length peer-reviewed manuscripts were identified. The number of publications increased over the time frame analyzed, with 48% focused on augmented repair. Rabbit was, by far, the most prevalent species utilized (46%), with dog (21%) and sheep (20%) being the next most common. Analysis of study descriptors revealed that most studies appropriately documented details of the animal used, the surgical approach, and defect and implant characteristics (e.g., 63% of studies identified clearly the defect size). In terms of outcome parameters, most studies carried out macroscopic (85%), histologic (90%), and healing/integration (83%) analyses of the meniscus. However, many studies did not provide further analysis beyond these fundamental measures, and less than 40% reported on the adjacent cartilage and synovium, as well as joint function. There is intense interest in the field of meniscus repair. However, given the current lack of guidance documentation in this area, preclinical animal models are not performed in a standardized fashion. The development of a "Best Practices" document would increase reproducibility and external validity of experiments, while accelerating advancements in translational research. Advancement is of paramount importance given the high prevalence of meniscal injuries and the paucity of effective repair or regenerative strategies.

Project description:BackgroundReconstruction is the gold standard treatment for medial ulnar collateral ligament (MUCL) injuries. However, recent studies show a successful and renewed interest in direct suture repair, particularly in young athletes. Repair augmentation with a suture tape may provide greater stability, enabling healing of the MUCL while protecting the repair at higher valgus loads.PurposeTo perform a systematic review and meta-analysis on whether MUCL repair with augmentation provides a similar biomechanical profile to the traditional MUCL reconstruction.Study designSystematic review.MethodsThe Cochrane Controlled Register of Trials, PubMed, Medline, and Embase were used to perform a systematic review and meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria with the following search terms: ("ulnar collateral ligament" OR "medial ulnar collateral ligament") AND ("internal brace" OR "augmentation" OR "suture tape"). Data pertaining to certain biomechanical properties (gap formation, failure to torque [ultimate load to failure], stiffness, degree of valgus opening, and modes of failure) were extracted. The pooled outcome data were analyzed by random- and fixed-effects models. A total of 203 abstracts were identified through the aforementioned databases.ResultsAfter abstract and full-text screening, 6 biomechanical studies were included. All were on cadaveric elbows, with 53 repairs with augmentation and 53 reconstructions compared. There were no differences between the 2 in regard to ultimate load to failure (standard mean difference [SMD], -0.34 N·m; 95% CI, -1.36 to 0.68; P = .51) and rotational stiffness (SMD, 0.26; 95% CI, -1.14 to 1.66; P = .72). Despite a trend in resistance to gapping with augmented repair, this was not significant (SMD, -0.53; 95% CI, -1.08 to 0.01; P = .06). Augmented repairs were more likely to fail by pullout or at the suture-tendon/anchor-suture interface (odds ratio [OR], 12.19; 95% CI, 4.17 to 35.62; P < .00001), while failure by fracture was more common with reconstruction (OR, 5.75; 95% CI, 2.07 to 15.99; P = .0008).ConclusionMUCL augmented repair establishes the required time-zero structural properties without the need for a tendon graft. However, future clinical studies are necessary to determine its true effectiveness as well as its success at higher levels of professional sport.

Project description:PurposeTo quantify healing rates and patient-reported outcome scores following repair of radial meniscus tears.MethodsPubMed, Scopus, and Embase databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria included: human subjects with meniscal tears, full-text English language, average follow-up of at 1 year, and publication after the 2000. Exclusion criteria included technical, biomechanical, and cadaveric studies. Study quality was assessed using Coleman Methodology Scores and Methodological Index for Non-Randomized Studies (MINORS) criteria.ResultsTwelve studies reported on the repair of 243 radial tears in 241 patients. The mean Modified Coleman Methodology Score was 46.8, range 26-60, with a mean level of evidence of 3.5. Arthroscopic techniques were used in all studies, with 1 study using an arthroscopic-assisted 2-tunnel trans-tibial pullout technique. The mean patient age was 32 years (11-71). The mean follow-up was 35 months (12 to 75.6). The average time to surgery was 10.9 months (0.5-22.4). Eight of the 12 studies reported concomitant anterior cruciate ligament (ACL) reconstruction, with 64% having concomitant ACL injury. The most common outcome measure was the Lysholm score, which improved from 47-68.9 preoperatively to 86.4-95.6 postoperatively. Tegner Activity Scale improved from 2.5-3.1 preoperatively to 4.7-6.7 postoperatively. Healing rates were reported via magnetic resonance imaging and second-look arthroscopy. Second-look arthroscopy was performed for a variety of indications, including removal of screw, washers or plates, dissatisfaction with original procedure, partial healing found on magnetic resonance imaging, or desire of the patient to know the true healing status before return to sport. Of those assessed, 62.0% had complete healing, 30.0% partial healing, and 8.0% failure to heal.ConclusionsPatient-reported outcomes of radial meniscus repair with and without ACL reconstruction are encouraging, with high patient-reported outcomes reported at final follow-up when compared with preoperative scores. Among all meniscus repairs assessed for healing, the majority demonstrated at least some healing with an overall low rate of failure.Level of evidenceIV; systematic review of level III-IV studies.

Project description:Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of blood glucose can damage multiple organs, including the brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities of diabetes. Despite the largely consistent link between diabetes and dementia, the underlying causes of neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders is neuroinflammation, a complex inflammatory process in the central nervous system for the most part orchestrated by microglial cells, the main representatives of the immune system in the brain. In this context, our research question aimed to understand how diabetes affects brain and/or retinal microglia physiology. We conducted a systematic search in PubMed and Web of Science to identify research items addressing the effects of diabetes on microglial phenotypic modulation, including critical neuroinflammatory mediators and their pathways. The literature search yielded 1327 records, including 18 patents. Based on the title and abstracts, 830 papers were screened from which 250 primary research papers met the eligibility criteria (original research articles with patients or with a strict diabetes model without comorbidities, that included direct data about microglia in the brain or retina), and 17 additional research papers were included through forward and backward citations, resulting in a total of 267 primary research articles included in the scoping systematic review. We reviewed all primary publications investigating the effects of diabetes and/or its main pathophysiological traits on microglia, including in vitro studies, preclinical models of diabetes and clinical studies on diabetic patients. Although a strict classification of microglia remains elusive given their capacity to adapt to the environment and their morphological, ultrastructural and molecular dynamism, diabetes modulates microglial phenotypic states, triggering specific responses that include upregulation of activity markers (such as Iba1, CD11b, CD68, MHC-II and F4/80), morphological shift to amoeboid shape, secretion of a wide variety of cytokines and chemokines, metabolic reprogramming and generalized increase of oxidative stress. Pathways commonly activated by diabetes-related conditions include NF-κB, NLRP3 inflammasome, fractalkine/CX3CR1, MAPKs, AGEs/RAGE and Akt/mTOR. Altogether, the detailed portrait of complex interactions between diabetes and microglia physiology presented here can be regarded as an important starting point for future research focused on the microglia-metabolism interface.

Project description:BackgroundDiabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia. It affects millions of people globally. In spite of many antidiabetic drugs that are available, an adequate level of control remains challenging. Hydroxychloroquine is an immunomodulatory drug that has been used for the treatment of malaria and autoimmune diseases. There is an emerging evidence that suggests its beneficial effect against diabetes mellitus. Therefore, this systematic review is aimed at discoursing the role of hydroxychloroquine against diabetes mellitus and its potential mechanisms of actions.MethodsA systematic and manual searching was carried out to retrieve relevant articles (preclinical and clinical studies) published from January 2014 to July 2019. Electronic databases including PubMed and Scopus as well as clinicaltrials.gov have been searched using different searching terms: "hydroxychloroquine," "diabetes mellitus," "hyperglycemia," and "insulin resistance." The MeSH terms (PubMed) and text words were combined with "AND" or "OR." In addition, manual searching of Google Engine and Google Scholar was conducted. Quality assessment of all the included studies was performed using CAMARADES (preclinical studies) and the Newcastle-Ottawa Scale and Cochrane Collaboration's tools (clinical studies).ResultsA total of eighteen studies (three experimental and fifteen clinical studies) were found to be eligible for the present systematic review. Among the included clinical studies (six randomized control trials, five observational studies, and four cohort studies), about 55,776 study participants were involved. Most of these studies showed significant improvement of lipid profile and insulin levels and substantial diminution of hemoglobin A1c, fasting plasma glucose, and postprandial blood glucose levels. Reduction in lysosomal degradation of the internal insulin-insulin receptor complex and enhancement in insulin sensitivity and adiponectin levels are some of the hypothesized mechanisms for the antidiabetic effect of hydroxychloroquine.ConclusionThe current review provides preliminary evidence for potential antidiabetic properties of hydroxychloroquine. Though the provided available data were promising, further clinical trials and mechanistic studies are needed to determine its long-term effects.

Dataset Information

Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies.

Publications

Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets