Metabolic cues are crucial for regulating haematopoietic stem and progenitor cells (HSPCs). However, the metabolic profile of human HSPCs remains poorly understood due to the limited number of cells and the scarcity of bone marrow samples. Here we present the integrated metabolome, lipidome and transcriptome of human adult HSPCs (lineage⁻, CD34⁺, CD38⁻) upon differentiation, ageing and acute myeloid leukaemia. The combination of low-input targeted metabolomics with our newly optimized low-input untargeted lipidomics workflow allows us to detect up to 193 metabolites and lipids from a starting material of 3,000 and 5,000 HSPCs, respectively. Among other findings, we observe elevated levels of the essential nutrient choline in HSPCs compared with downstream progenitors, which decline upon ageing and further decrease in acute myeloid leukaemia. Functionally, we show that choline supplementation fuels lipid production in HSPCs and enhances stemness. Overall, our study provides a comprehensive resource identifying metabolic changes that can be utilized to promote and enhance human stem cell function.

Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field.

Chondrosarcoma (CHS) are heterogenous, but as a whole, represent the second most common primary malignant bone tumor entity. Although knowledge on tumor biology has grown exponentially during the past few decades, surgical resection remains the gold standard for the treatment of these tumors, while radiation and differentiated chemotherapy do not result in sufficient cancer control. An in-depth molecular characterization of CHS reveals significant differences compared to tumors of epithelial origin. Genetically, CHS are heterogenous, but there is no characteristic mutation defining CHS, and yet, IDH1 and IDH2 mutations are frequent. Hypovascularization, extracellular matrix composition of collagen, proteoglycans, and hyaluronan create a mechanical barrier for tumor suppressive immune cells. Comparatively low proliferation rates, MDR-1 expression and an acidic tumor microenvironment further limit therapeutic options in CHS. Future advances in CHS therapy depend on the further characterization of CHS, especially the tumor immune microenvironment, for improved and better targeted therapies.

Background Congenital hip dislocation (luxation) has an incidence of 0.4 – 0.7% and is regarded as a prearthrotic deformity. Thus, if not being diagnosed and treated at a very early age, extensive surgical measures are inevitable in childhood and early adulthood.Methods In the time between 01/2013 and 02/2019 we performed 28 600 hips sonographies in babies as part of general screening measures at U2 or U3. There were 71 instable, dysplastic or dislocated hips diagnosed that were treated by arthrographic, closed reduction. After a hip spica cast was applied, reposition was controlled by MRI, estimating the acetabular head index (ACI), the head coverage index (HCI) as well as the femoral headʼs sphericity or by sonography using the Graf method.Results Overall success rate was 91.6% for primary closed reduction. Patients with primarily irreducible hips were significantly older (p < 0.003) than patients with primarily successful reducible hips. Congenital dislocated hips had significantly higher ACIs (p < 0.001) and HCIs (p = 0.03) as well as significantly less well rounded femoral heads (sphericity; p < 0.001) compared to stable hips.Conclusion Early diagnosis and treatment of congenital dislocated hips by closed reduction is essential for a sufficient and regular maturation of the hips without further surgical interventions.

Purpose: Sonographic hip examination according to Graf is widely accepted standard for diagnosing developmental dysplastic hips (DDH) but it is criticized for alleged intra- and interobserver variations. This review was conducted to evaluate whether objective quality criteria according to the Graf method are fulfilled within scientific literature.Methods: A systematic literature search on Pubmed was performed using the search string: [(DDH) OR (Hip dysplasia)] AND (Graf). Studies suitable by title, abstract, manuscript, containing an image of sonographic hip examination and online accessibility were included into analysis.Results: 131 studies were included into final analysis. Only 68 (51.9%) presented correct sonographic images according Graf’s criteria. 98 (74.8%) studies plotted alpha-angles (angle between bony roof line and base line) but only 85 (64.8%) studies beta-angles (angle between cartilage roof line and base line). Studies were contributed from 25 countries.Conclusion: Assumingly, skepticism regarding the Graf method is based on user errors and insufficient application of the Graf quality assessment algorithm resulting in high intra- and interobserver variations. When performed correctly, the Graf method is of high diagnostic value.

Aim of the study The present study aimed to identify risk factors for unsuccessful CR. Introduction Closed reduction (CR) represents the gold standard for treatment of developmental dysplasia of the hip (DDH), but to a minor percentage, it fails to reduce dysplastic hips successfully. Methods Seventy-three dysplastic hips underwent closed reduction and post-interventional MRI of the pelvis. MRIs were evaluated for successful reduction of the hip, volumes of femoral heads, and acetabular diameter. Initial treatment results were correlated to AC angles at two years of follow-up. Contralateral, healthy hips served as control. Results Out of 73 instable, dysplastic hips, there were nine cases of CR failure. These cases showed significantly increased femoral head volumes (p = 0.002) and a significantly (p = 0.02) larger ratio of femoral head volume to acetabular opening area. There was no significant difference (p = 0.15) in acetabular diameter between both groups. At two years of follow-up, AC angles were significantly (p = 0.003) larger and pathologic in cases of CR failure. Conclusion Exclusive enlargement of the femoral head is a risk factor for unsuccessful reduction and its ratio to the acetabular opening surface is predictive for CR success in DDH.