Eva Johanna Kubosch

The trans-well coculture of human synovial mesenchymal stem cells with chondrocytes leads to self-organization, chondrogenic differentiation, and secretion of TGFβ

BackgroundSynovial mesenchymal stem cells (SMSC) possess a high chondrogenic differentiation potential, which possibly supports natural and surgically induced healing of cartilage lesions. We hypothesized enhanced chondrogenesis of SMSC caused by the vicinity of chondrocytes (CHDR).MethodsHuman SMSC and CHDR interactions were investigated in an in-vitro trans-well monolayer coculture over a time period of up to 21 days. Protein expression was analyzed using histology, immunostaining, or enzyme-linked immunosorbent assay. Additionally, mRNA expression was assessed by quantitative PCR.ResultsAfter 7 days, phase-contrast microscopy revealed cell aggregation of SMSC in coculture with CHDR. Afterwards, cells formed spheres and lost adherence. However, this phenomenon was not observed when culturing SMSC alone. Fluorescence labeling showed concurrent collagen type II expression. Addition of transforming growth factor beta (TGFβ) to the cocultures induced SMSC aggregation in less time and with higher intensity. Additionally, alcian blue staining demonstrated enhanced glycosaminoglycan expression around SMSC aggregates after 1 and 2 weeks. Although TGFβ mRNA was expressed in all SMSC, the protein was measured with constantly increasing levels over 21 days only in supernatants of the cocultures. Considering the enhanced mRNA levels following supplementation with TGFβ, a positive feedback mechanism can be supposed. In line with the development of a chondrogenic phenotype, aggrecan mRNA expression increased after 7 and 14 days in the cocultures with and without TGFβ. Coculture conditions also amplified collagen type II mRNA expression after 2 weeks without and already after 1 week with TGFβ. There was no difference in collagen type I and type X expression between SMSC alone and the coculture with CHDR. Expression of both collagens increased following addition of TGFβ. mRNA data correlated with the intensity of immunofluorescence staining.ConclusionsParacrine effects of CHDR induce a chondrogenic phenotype in SMSC possibly mimicking joint homeostasis. Coculture approaches may lead to a better understanding of cellular interactions with potential implications for cartilage repair procedures.

In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation — a comparison

PurposeThe use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources.MethodsVia clinically validated flow cytometry analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC).ResultsPrimary, human BMSC and SDSC revealed similar adipogenic, osteogenic, and chondrogenic differentiation potential and stem cell marker expression. However, the expression of the chondrogenic markers Col2 and ACAN was statistically significant higher in SDSC. CHDR and SDSC expressed ACAN and CD44 equally, but Col2 was expressed more strongly on the SDSC surface. The marker expression of SDSC from osteoarthritic joints (Kellgren-Lawrence score ≥3) versus normal knees (Kellgren-Lawrence score ≤2) did not differ. Similarly, there was no difference between temporarily frozen and fresh SDSC. Col2 and ACAN surface expression declined with further passaging, whereas CD44 remained unchanged. We observed the same effect after reducing the serum content. When comparing CHDR for ACI with SDSC of the same passage (P2/3), both Col2 and ACAN, correlating with clinical outcome, were expressed higher in SDSC.ConclusionsIn summary, SDSC demonstrated high differentiation potential and a stable chondrogenic phenotype. They might therefore be better suitable for ACI than BMSC or passaged CHDR.

GERMAN TRANSLATION AND CONTENT VALIDATION OF THE OSTRC QUESTIONNAIRE ON OVERUSE INJURIES AND HEALTH PROBLEMS

Objective The aim of this study was to translate, culturally adapt and validate the Oslo Sports Trauma Research Centre (OSTRC) Questionnaire on Health Problems into the German context. Methods A slightly modified back-translation method was used to translate the questionnaire. Validation was done in 24 high-level Paralympic athletes followed over 20 consecutive weeks. Results The translated version of the questionnaire showed a very high internal consistency and good test–retest reliability (Cronbachs α 0.92, intraclass correlation coefficient 0.91). Additionally, we observed high acceptance and compliance from our cohort of athletes, whose mean weekly response rate was 91.5%. Overall, 114 training days were lost because of illness or injury within the 20 weeks and, on average, 5 athletes per week (20.8%) reported health problems. Conclusions This study demonstrates that the translated German version of the OSTRC Questionnaire is a reliable and valid tool with high internal consistency for the medical monitoring of German athletes. The OSTRC-G now offers the opportunity for a continued surveillance of high-level German athletes.

Work–family conflict and neck and back pain in surgical nurses

Objective. Surgical nurses’ work is physically and mentally demanding, possibly leading to work–family conflict (WFC). The current study tests WFC to be a risk factor for neck and lower back pain (LBP). Job influence and social support are tested as resources that could buffer the detrimental impact of WFC. Methods. Forty-eight surgical nurses from two university hospitals in Germany and Switzerland were recruited. WFC was assessed with the Work–Family Conflict Scale. Job influence and social support were assessed with the Copenhagen Psychosocial Questionnaire, and back pain was assessed with the North American Spine Society Instrument. Results. Multiple linear regression analyses confirmed WFC as a significant predictor of cervical pain (β = 0.45, p < 0.001) and LBP (β = 0.33, p = 0.012). Job influence and social support did not turn out to be significant predictors and were not found to buffer the impact of WFC in moderator analyses. Conclusion. WFC is likely to affect neck and back pain in surgery nurses. Work–life interventions may have the potential to reduce WFC in surgery nurses.

Quantitative work demands, emotional demands, and cognitive stress symptoms in surgery nurses

Abstract In surgery, cognitive stress symptoms, including problems in concentrating, deciding, memorising, and reflecting are risks to patient safety. Recent evidence points to social stressors as antecedents of cognitive stress symptoms in surgery personnel. The current study tests whether cognitive stress symptoms are positively associated with emotional abuse, emotional- and task-related demands and resources in surgery work. Forty-eight surgery nurses from two hospitals filled out the Copenhagen Psychosocial Questionnaire in its German version. Task-related and emotional demands were positively related to cognitive stress symptoms. In a stepwise, multiple, linear regression of cognitive stress symptoms on task-related and emotional demands, emotional abuse and emotional demands were unique predictors (p < .05). Efforts to increase patient safety should address emotional abuse, emotional demands, and, therefore, communication and cooperation team climate in surgery personnel.

The Lumbar Spine as a Dynamic Structure Depicted in Upright MRI.

AbstractSpinal canal stenosis is a dynamic phenomenon that becomes apparent during spinal loading. Current diagnostic procedures have considerable short comings in diagnosing the disease to full extend, as they are performed in supine situation. Upright MRI imaging might overcome this diagnostic gap.This study investigated the lumbar neuroforamenal diameter, spinal canal diameter, vertebral body translation, and vertebral body angles in 3 different body positions using upright MRI imaging.Fifteen subjects were enrolled in this study. A dynamic MRI in 3 different body positions (at 0° supine, 80° upright, and 80° upright + hyperlordosis posture) was taken using a 0.25 T open-configuration scanner equipped with a rotatable examination bed allowing a true standing MRI.The mean diameter of the neuroforamen at L5/S1 in 0° position was 8.4 mm on the right and 8.8 mm on the left, in 80° position 7.3 mm on the right and 7.2 mm on the left, and in 80° position with hyperlordosis 6.6 mm (P < 0.05) on the right and 6.1 mm on the left (P < 0.001).The mean area of the neuroforamen at L5/S1 in 0° position was 103.5 mm2 on the right and 105.0 mm2 on the left, in 80° position 92.5 mm2 on the right and 94.8 mm2 on the left, and in 80° position with hyperlordosis 81.9 mm2 on the right and 90.2 mm2 on the left.The mean volume of the spinal canal at the L5/S1 level in 0° position was 9770 mm3, in 80° position 10600 mm3, and in 80° position with hyperlordosis 9414 mm3.The mean intervertebral translation at level L5/S1 was 8.3 mm in 0° position, 9.9 mm in 80° position, and 10.1 mm in the 80° position with hyperlordosis.The lordosis angle at level L5/S1 was 49.4° in 0° position, 55.8° in 80° position, and 64.7 mm in the 80° position with hyperlordosis.Spinal canal stenosis is subject to a dynamic process, that can be displayed in upright MRI imaging. The range of anomalies is clinically relevant and dynamic positioning of the patient during MRI can provide essential diagnostic information which are not attainable with other methods.

The Potential for Synovium-derived Stem Cells in Cartilage Repair

BACKGROUND Articular cartilage defects often result in pain, loss of function and finally osteoarthritis. Developing cell-based therapies for cartilage repair is a major goal of orthopaedic research. Autologous chondrocyte implantation is currently the gold standard cell-based surgical procedure for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. OBJECTIVE Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current knowledge on the chondrogenic potential for synovial stem cells in regard to cartilage repair purposes. RESULTS A literature search was carried out identifying 260 articles in the databases up to January 2017. Several in vitro and initial animal in vivo studies of cartilage repair using synovia stem cell application showed encouraging results. Since synvoium-derived stem cells are located in the direct vicinity of cartilage and cartilage lesions these cells might even contribute to natural cartilage regeneration. The only one published human in vivo study with 10 patients revealed good results concerning postoperative outcome, MRI, and histologic features after a two-stage implantation of synovial stem cells into an isolated cartilage defect of the femoral condyle. CONCLUSION Synovium-derived stem cells possess great chondrogenic potential and showed encouraging results for cartilage repair purposes. Furthermore, synovial stem cells play an important role in joint homeostasis and possibly in natural cartilage repair. Further studies are needed to elucidate the interplay of synovial stem cells and chondrocytes, and the promising role of synovium-derived stem cells in cartilage tissue engineering.

The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy-a systematic review including meta-analysis

Chronic painful Achilles tendinopathy (AT) is a common disorder among athletes. Sclerotherapy (ST) and prolotherapy (PT) are two promising options among the numerous other conservative therapies. As their efficacy and potential adverse effects (AE) are still unclear, we systematically searched, analyzed, and synthesized the available literature on ST and PT for treating AT. Electronic databases, Google Scholar and articles’ reference lists were searched according to PRISMA guidelines. Eligibility criteria were set up according to the PICOS‐scheme including human and animal studies. Three authors independently reviewed the results and evaluated methodological quality (Coleman Methodology Score and Cochrane Risk of Bias Assessment). The initial search yielded 1104 entries. After screening, 18 articles were available for qualitative synthesis, six of which were subjected to meta‐analysis. The mean Coleman Score of the 13 human studies was 50. Four RCTs were ranked as having a low risk of selection bias. Three of those reported a statistically significant drop in the visual analog scale (VAS) score, one a significant increase in the VISA‐A Score. 12 of 13 human studies reported positive results in achieving pain relief and patient satisfaction, whereas only one studys finding differed. Meta‐analysis revealed an unambiguous result in favor of the intervention (weighted mean difference D=−4.67 cm, 95% CI −5.56 to −3.76 cm [P<.001]). Only one serious AE and two minor AEs were reported in the entire literature. This systematic review suggests that ST and PT may be effective treatment options for AT and that they can be considered safe. Long‐term studies and RCTs are still needed to support their recommendation.

Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions

Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes (p < 0.05). This correlated with a more chondrogenic structure and higher proteoglycan expression, resulting in a lower OARSI score (p < 0.05). The repair tissue of all groups expressed comparable amounts of the collagen types I, II, and X. Cartilage regeneration following matrix-associated implantation using allogenic undifferentiated synovium-derived stem cells in a defect model in rabbits showed similar macroscopic results and collagen composition compared to amplified chondrocytes; however, biomechanical characteristics and histological scoring were inferior.

Preoperative Assessment of Neural Elements in Lumbar Spinal Stenosis by Upright Magnetic Resonance Imaging: An Implication for Routine Practice?

Introduction Lumbar spinal stenosis (LSS) is a kinetic-dependent disease typically aggravating during spinal loading. To date, assessment of LSS is usually performed with magnetic resonance imaging (MRI). However, conventional supine MRI is associated with significant drawbacks as it does not truly reflect physiological loads, experienced by discoligamentous structures during erect posture. Consequently, supine MRI often fails to reveal the source of pain and/or disability caused by LSS. The present study sought to assess neural dimensions via MRI in supine, upright, and upright-hyperlordotic position in order to evaluate the impact of patient positioning on neural narrowing. Therefore, radiological measures such as neuroforaminal dimensions, central canal volume, sagittal listhesis, and lumbar lordosis at spinal level L4/5 were extracted and stratified according to patient posture. Materials and methods Overall, 10 subjects were enclosed in this experimental study. MRI was performed in three different positions: (1) 0° supine (SP), (2) 80° upright (UP), and (3) 80° upright + hyperlordotic (HY) posture. Upright MRI was conducted utilizing a 0.25T open-configuration scanner equipped with a rotatable examination bed allowing for true standing MRI. Radiographic outcome of upright MRI imaging was extracted and evaluated according to patient positioning. Results Upright MRI-based assessment of neural dimensions was successfully accomplished in all subjects. Overall, radiographic parameters revealed a significant decrease of neural dimensions from supine to upright position: Specifically, mean foraminal area decreased from SP to UP by 13.3% (P ≤ 0.05) as well as from SP to HY position by 21% (P ≤ 0.05). Supplementation of hyperlordosis did not result in additional narrowing of neural elements (P ≥ 0.05). Furthermore, central canal volume revealed a decrease of 7% at HY and 8% at UP compared to SP position (P ≥ 0.05). Assessment of lumbar lordosis yielded in a significant increase when assessed at HY (+22.1%) or UP (+8.7%) compared to SP (P ≤ 0.05). Conclusions Our data suggest that neuroforaminal dimensions assessed by conventional supine MRI are potentially overestimated in patients with LSS. Especially, in patients having occult disease not visualized on conventional imaging modalities, upright MRI allows for a precise, clinically relevant, and at the same time non-invasive evaluation of neural elements in LSS when neural decompression is considered.