Trauma Department, Experimental Trauma Surgery – Laboratory for Musculoskeletal Trauma and Regenerative Therapies Hannover Medical School (MHH), Carl-Neuberg-Str.1, 30625 Hannover, Germany
Dr. Claudia Neunaber
Trauma Department, Experimental Trauma Surgery – Laboratory for Musculoskeletal Trauma and Regenerative Therapies Hannover Medical School (MHH), Carl-Neuberg-Str.1, 30625 Hannover, Germany
Human bone marrow‐derived stromal cells (hBMSCs) derived from the adult organism hold great promise for diverse settings in regenerative medicine. Therefore a more complete understanding of hBMSC biology to fully exploit the cells’ potential for clinical settings is important. The protein CD24 has been reported to be involved in a diverse range of processes such as cancer, adaptive immunity, inflammation, and autoimmune diseases in other cell types. Its expression in hBMSCs, which has not yet been analyzed, may add an important aspect in the understanding of hBMSC biology. The present study therefore analyzes the expression, regulation, and functional implication of the surface protein CD24 in hBMSCs. Methods used are stimulation studies with TGF beta as well as shRNA‐mediated knockdown and overexpression of CD24 followed by microarray, immunocytochemistry, and flow cytometric analyses. To our knowledge, we demonstrate for the first time that the expression of CD24 is an inherent property of hBMSCs. Importantly, the data links the upregulation of CD24 to the adoption of a myofibroblast‐like gene expression pattern in hBMSCs. We demonstrate that CD24 is an important modulator in transforming growth factor beta 3 (TGFβ3) signaling with a reciprocal regulatory relationship between these two proteins.
1 January 2011 in Recent Patents on Inflammation & Allergy Drug Discovery
Due to improved treatment strategies mortality in multiple trauma patients has been decreased over the last decades. However, posttraumatic complications like sepsis and subsequent multiple organ dysfunction syndrome (MODS) remain a major problem on intensive care units following major trauma. The clinical course after multiple trauma depends on the balance or imbalance of the pro- and anti-inflammatory immune response. The predominance of the proinflammatory response leads to the “Systemic Inflammatory Response Syndrome” (SIRS), whereas the “Compensatory Anti-inflammatory Response Syndrome” (CARS) might result in immune suppression with an enhanced risk for infectious complications. Both, SIRS and CARS, play a pivotal role in the development of sepsis and the “Multiple Organ Dysfunction Syndrome” (MODS). A gender dimorphism in the host response after multiple trauma and sepsis has already been described. In experimental as well as clinical studies, a protective effect of female sex hormones and precursors like androstenediol has been revealed. Moreover, blockade of androgen receptors and the inhibition of dihydrotestosterone (DHT) synthesis were shown to provide beneficial effects on the immune response. Beside sex hormones, modulation of the Toll Like Receptor (TLR) pathway by macrophage-activating lipopeptide-2 (MALP-2) has sufficiently been described. Furthermore, hydrogen sulfide (H2S) and substance P have recently been revealed important for proinflammatory action in animal models of inflammation. Thus, these agents might be potential candidates for new treatment strategies in septic patients in order to improve the still unsatisfactory outcome of multiple trauma patients. If applicable, patents of each described agent are provided within the text.
Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for cell-based therapies. Growing evidence has indicated that overweight/obesity can change the bone marrow microenvironment, which affects some properties of BMSCs. As the overweight/obese population rapidly increases, they will inevitably become a potential source of BMSCs for clinical application, especially when receiving autologous BMSC transplantation. Given this situation, the quality control of these cells has become particularly important. Therefore, it is urgent to characterize BMSCs isolated from overweight/obese bone marrow environments. In this review, we summarize the evidence of the effects of overweight/obesity on the biological properties of BMSCs derived from humans and animals, including proliferation, clonogenicity, surface antigen expression, senescence, apoptosis, and trilineage differentiation, as well as the underlying mechanisms. Overall, the conclusions of existing studies are not consistent. Most studies demonstrate that overweight/obesity can influence one or more characteristics of BMSCs, while the involved mechanisms are still unclear. Moreover, insufficient evidence proves that weight loss or other interventions can rescue these qualities to baseline status. Thus, further research should address these issues and prioritize developing methods to improve functions of overweight- or obesity-derived BMSCs.