Tissue engineering is a promising alternative to current full thickness circumferential esophageal replacement methods. The aim of our study was to develop a clinical grade Decellularized Human Esophagus (DHE) for future clinical applications. After decontamination, human esophagi from deceased donors were placed in a bioreactor and decellularized with sodium dodecyl sulfate (SDS) and ethylendiaminetetraacetic acid (EDTA) for 3 days.
View Article and Find Full Text PDFChanges in lymphocyte production patterns occurring across human ontogeny remain poorly defined. In this study, we demonstrate that human lymphopoiesis is supported by three waves of embryonic, fetal, and postnatal multi-lymphoid progenitors (MLPs) differing in CD7 and CD10 expression and their output of CD127 early lymphoid progenitors (ELPs). In addition, our results reveal that, like the fetal-to-adult switch in erythropoiesis, transition to postnatal life coincides with a shift from multilineage to B lineage-biased lymphopoiesis and an increase in production of CD127 ELPs, which persists until puberty.
View Article and Find Full Text PDFType 2 diabetes is associated with an inflammatory phenotype in the pancreatic islets. We previously demonstrated that proinflammatory cytokines potently activate the tryptophan/kynurenine pathway (TKP) in INS-1 cells and in normal rat islets. Here we examined: (1) the TKP enzymes expression in the diabetic GK islets; (2) the TKP enzymes expression profiles in the GK islets before and after the onset of diabetes; (3) The glucose-stimulated insulin secretion (GSIS) in vitro in GK islets after KMO knockdown using specific morpholino-oligonucleotides against KMO or KMO blockade using the specific inhibitor Ro618048; (4) The glucose tolerance and GSIS after acute in vivo exposure to Ro618048 in GK rats.
View Article and Find Full Text PDFBackground: Tissue engineering is an attractive alternative to conventional esophageal replacement techniques using intra-abdominal organs which are associated with a substantial morbidity. The objective was to evaluate the feasibility of esophageal replacement by an allogenic decellularized esophagus in a porcine model. Secondary objectives were to evaluate the benefit of decellularized esophagus recellularization with autologous bone marrow mesenchymal stromal cells and omental maturation of the decellularized esophagus.
View Article and Find Full Text PDFIn pathologies of the esophagus such as esophageal atresia, cancers, and caustic injuries, methods for full thickness esophageal replacement require the sacrifice of healthy intra-abdominal organs such as the stomach and the colon and are associated with high morbidity, mortality, and poor functional results. To overcome these problems, tissue engineering methods are developed to create a substitute with scaffolds and cells. The aim of this study was to develop a simple and safe decellularization process in order to obtain a clinical grade esophageal extracellular matrix.
View Article and Find Full Text PDFTissue engineering appears promising as an alternative technique for esophageal replacement. Mesenchymal stem cells (MSCs) could be of interest for esophageal regeneration. Evaluation of the ability of an acellular matrix seeded with autologous MSCs to promote tissue remodeling toward an esophageal phenotype after circumferential replacement of the esophagus in a mini pig model.
View Article and Find Full Text PDFAfter 30 years of hematopoietic stem cell use for various indications, umbilical cord blood is considered as an established source of cells with marrow and postmobilization peripheral blood. The limited number of cells still remains a problematic element restricting their use, especially in adults who require to be grafted with a higher cell number. Improving the quality of harvested cord blood, at least in terms of volume and amount of cells, is essential to decrease the number of discarded units.
View Article and Find Full Text PDFMany of the components that regulate the circadian clock have been identified in organisms and humans. The influence of circadian rhythm (CR) on the regulation of stem cells biology began to be evaluated. However, little is known on the role of CR on human mesenchymal stem cell (hMSCs) properties.
View Article and Find Full Text PDFBackground: Esophageal replacement by the colon or the stomach for malignant and nonmalignant esophageal diseases exposes to significant morbidity and mortality. In this setting, tissue engineering seems to be a seductive alternative.
Methods: In a porcine model, we performed a 5-cm-long circumferential replacement of the cervical esophagus by a tubulized acellular matrix (small intestinal submucosa) cellularized with autologous skeletal myoblasts and covered by a human amniotic membrane seeded with autologous oral epithelial cells.
Introduction: Tissue engineering represents a promising approach for esophageal replacement, considering the complexity and drawbacks of conventional techniques.
Aim: To create the components necessary to reconstruct in vitro or in vivo an esophageal wall, we analyzed the feasibility and the optimal conditions of human and pig skeletal myoblast (HSM and PSM) and porcine oral epithelial cell (OEC) culture on biologic scaffolds.
Materials And Methods: PSM and HSM were isolated from striated muscle and porcine OECs were extracted from oral mucosa biopsies.
In human skeletal muscle, myoblasts represent the main population of myogenic progenitors. We previously showed that, beside their myogenic differentiation capacities, myoblasts also differentiate towards osteogenic and chondrogenic lineages, some properties generally considered being hallmarks of mesenchymal stem cells (MSCs). MSCs are also characterized by their immunosuppressive potential, through cell-cell contacts and soluble factors, including prostaglandin E-2 (PGE-2), transforming growth factor-β1 (TGF-β1), interleukine-10, or indoleamine 2,3-dioxygenase.
View Article and Find Full Text PDFBackground: Esophageal replacement is a challenging problem requiring complex reconstruction. In response to the recent success of tracheal replacement by fresh allogenic aorta in humans, we assessed in a pig model the feasibility of circumferential segmental esophageal replacement by a fresh aortic allograft.
Methods: A 4-cm long aortic allograft was interposed after a circumferential 2-cm long resection of the cervical esophagus in 18 minipigs.
In human physiology and animal models, bone marrow mesenchymal stem cells (MSCs) exert an immunosuppressive role in both in vitro and in vivo experiments. However, cellular and molecular mechanisms involved in this process are not clear and remain largely elusive. Several studies have suggested the implication of cell-cell contacts or soluble factors including transforming growth factor-b1 (TGF-b1), interleukin-10 (IL-10), indoleamine 2,3-dioxygenase (IDO), or human leukocyte antigen-G (HLA-G).
View Article and Find Full Text PDF