Evaluating the Effect of Hypoxia on Human Adult Mesenchymal Stromal Cell Chondrogenesis In Vitro: A Systematic Review.

Human adult mesenchymal stromal cells (MSCs) from a variety of sources may be used to repair defects in articular cartilage by inducing them into chondrogenic differentiation. The conditions in which optimal chondrogenic differentiation takes place are an area of interest in the field of tissue engineering. Chondrocytes exist in vivo in a normally hypoxic environment and thus it has been suggested that exposing MSCs to hypoxia may also contribute to a beneficial effect on their differentiation. There are two main stages in which MSCs can be exposed to hypoxia, the expansion phase when cells are cultured, and the differentiation phase when cells are induced with a chondrogenic medium. This systematic review sought to explore the effect of hypoxia at these two stages on human adult MSC chondrogenesis in vitro. A literature search was performed on PubMed, EMBASE, Medline via Ovid, and Cochrane, and 24 studies were ultimately included. The majority of these studies showed that hypoxia during the expansion phase or the differentiation phase enhances at least some markers of chondrogenic differentiation in adult MSCs. These results were not always demonstrated at the protein level and there were also conflicting reports. Studies evaluating continuous exposure to hypoxia during the expansion and differentiation phases also had mixed results. These inconsistent results can be explained by the heterogeneity of studies, including factors such as different sources of MSCs used, donor variability, level of hypoxia used in each study, time exposed to hypoxia, and differences in culture methodology.

Quantitative analysis of the ACL and PCL using T1rho and T2 relaxation time mapping: an exploratory, cross-sectional comparison between OA and healthy control knees.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) methods such as T1rho and T2 mapping are sensitive to changes in tissue composition, however their use in cruciate ligament assessment has been limited to studies of asymptomatic populations or patients with posterior cruciate ligament tears only. The aim of this preliminary study was to compare T1rho and T2 relaxation times of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) between subjects with mild-to-moderate knee osteoarthritis (OA) and healthy controls. METHODS: A single knee of 15 patients with mild-to-moderate knee OA (Kellgren-Lawrence grades 2-3) and of 6 age-matched controls was imaged using a 3.0 T MRI. Three-dimensional (3D) fat-saturated spoiled gradient recalled-echo images were acquired for morphological assessment and T1ρ- and T2-prepared pseudo-steady-state 3D fast spin echo images for compositional assessment of the cruciate ligaments. Manual segmentation of whole ACL and PCL, as well as proximal / middle / distal thirds of both ligaments was carried out by two readers using ITK-SNAP and mean relaxation times were recorded. Variation between thirds of the ligament were assessed using repeated measures ANOVAs and differences in these variations between groups using a Kruskal-Wallis test. Inter- and intra-rater reliability were assessed using intraclass correlation coefficients (ICCs). RESULTS: In OA knees, both T1rho and T2 values were significantly higher in the distal ACL when compared to the rest of the ligament with the greatest differences in T1rho (e.g. distal mean = 54.5 ms, proximal = 47.0 ms, p < 0.001). The variation of T2 values within the PCL was lower in OA knees (OA: distal vs middle vs proximal mean = 28.5 ms vs 29.1 ms vs 28.7 ms, p = 0.748; Control: distal vs middle vs proximal mean = 26.4 ms vs 32.7 ms vs 33.3 ms, p = 0.009). ICCs were excellent for the majority of variables. CONCLUSION: T1rho and T2 mapping of the cruciate ligaments is feasible and reliable. Changes within ligaments associated with OA may not be homogeneous. This study is an important step forward in developing a non-invasive, radiological biomarker to assess the ligaments in diseased human populations in-vivo.

Blood transfusion demands in a tertiary otolaryngology, head and neck centre: A 5-year retrospective cohort study.

OBJECTIVES: To retrospectively analyse and report the utilisation of red blood cell (RBC) transfusion in a tertiary otolaryngology, head and neck centre in the United Kingdom. BACKGROUND: Twenty-seven per cent of RBC transfusions were for surgical indications in a 2014 England and North Wales survey. Currently, there is limited literature on RBC transfusions in Otolaryngology. METHODS/MATERIALS: All inpatients admitted primarily under the care of the Otolaryngology, Head and Neck service between January 2015 and December 2019 were analysed. The primary outcomes of interest were number of units of RBC transfused over 5 years and distribution across clinical indications. Secondary outcome measure was cost of RBC transfusions over the same time period. RESULTS: Most patients receiving transfusions are aged in their sixth and seventh decades. Epistaxis patients utilised 105 RBC units over the 5 years (56% of total RBC units) with emergency epistaxis accounting for 78% of use. Post-operative Head & Neck Cancer surgery with and without reconstruction required 47 RBC units over 5 years (25% of total RBC units). The mean cost incurred by the department over the 5-year period was £6171.49 (SD 1460.25). The cost has fallen by over £2000 over the 5-year period. CONCLUSION: Blood transfusion use has fluctuated over the last 5 years. Epistaxis and post-operative Head and Neck cancer cases account for significant use compared with other patient groups. Prehabilitation strategies will add value towards mitigating future consumption of RBC.

Evaluating the Effect of Non-cellular Bioactive Glass-Containing Scaffolds on Osteogenesis and Angiogenesis in in vivo Animal Bone Defect Models.

The use of bone scaffolds to replace injured or diseased bone has many advantages over the currently used autologous and allogeneic options in clinical practice. This systematic review evaluates the current evidence for non-cellular scaffolds containing bioactive glass on osteogenesis and angiogenesis in animal bone defect models. Studies that reported results of osteogenesis via micro-CT and results of angiogenesis via Microfil perfusion or immunohistochemistry were included in the review. A literature search of PubMed, EMBASE and Scopus was carried out in November 2019 from which nine studies met the inclusion and exclusion criteria. Despite the significant heterogeneity in the composition of the scaffolds used in each study, it could be concluded that scaffolds containing bioactive glass improve bone regeneration in these models, both by osteogenic and angiogenic measures. Incorporation of additional elements into the glass network, using additives, and using biochemical factors generally had a beneficial effect. Comparing the different compositions of non-cellular bioactive glass containing scaffolds is however difficult due to the heterogeneity in bioactive glass compositions, fabrication methods and biochemical additives used.

Are the Biological and Biomechanical Properties of Meniscal Scaffolds Reflected in Clinical Practice? A Systematic Review of the Literature.

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. This was done by only including studies that assessed clinical outcome and used a scale to assess both integrity of the scaffold and its effects on articular cartilage via MRI. A search was performed on PubMed, EMBASE, Scopus and clinicaltrials.gov. 2457 articles were screened, from which eight studies were selected: four used Actifit, three used CMI and one compared the two. All studies reported significant improvement in at least one clinical outcome compared to baseline. Some studies suggested that the scaffolds appeared to show porosity, mature, resorb and/or have possible chondroprotective effects, as assessed by MRI. The evidence for clinical translation is limited by differences in study methodology and small sample sizes, but is promising in terms of improving clinical outcomes in the short to mid-term. Higher level evidence, with MRI and histological evaluation of the scaffold and articular cartilage, is now needed to further determine whether these scaffolds exhibit these useful properties.

Evaluating the Current Literature on Treatments Containing Adipose-Derived Stem Cells for Osteoarthritis: a Progress Update.

PURPOSE OF REVIEW: Recent studies have investigated the effect of treatments containing adipose-derived mesenchymal stem cells (ADMSCs) on human osteoarthritis. These have mostly used biologic adjuvants which may influence results. Thus, the purpose of this systematic review is to evaluate the current literature on these treatments when used in isolation. RECENT FINDINGS: Five studies in this review used cultured ADMSCs, while four studies used stromal vascular fraction and three used micro-fragmented adipose tissue to deliver ADMSCs. No studies reported serious treatment-related adverse effects and all reported improvements in clinical measures for at least one dose. This was not necessarily reflected in imaging evaluations nor were improvements always maintained. Current low-level evidence is limited due to variability in study methodology but indicates that treatments containing ADMSCs, when used in isolation, are safe and have the potential to reduce pain and improve function. Randomized controlled trials are now needed.