(see Ref. complement the malignant cell, endothelial cell, and stem cell/progenitor cell sections. Seven new CD numbers were assigned to antibodies included in this section at the HLDA 8 Workshop meeting held during December 2004. 1. Introduction 1.1. What are stromal cells? Two broad historical definitions of stromal cells exist. The first is that they are cells of mesenchymal origin that are non-epithelium, non-endothelium, and non-haematopoietic. The second is that they are the cells within the stroma and therefore include fibroblasts, endothelial cells, and tissue resident leukocytes. Within both these definitions, some stromal cells, particularly leukocytes and endothelial cells, have been covered by previous HLDA workshops. However, fibroblasts have not been previously covered and as a consequence it is these cells that have been the focus of the stromal cell section in HLDA8. 1.2. What is a fibroblast? The most abundant cells of the stroma are fibroblasts, which are responsible for the synthesis and remodelling of extracellular matrix components. In addition, their ability to produce and respond to growth factors allows reciprocal interactions with other stromal cell types, and with adjacent epithelial and Tebanicline hydrochloride endothelial structures. As a consequence, fibroblasts play a critical role during tissue development and homeostasis, and Tebanicline hydrochloride are often described as using a sentinel or landscaping function. Moreover, these functions contribute to the pathology of many diseases either directly for example by overproduction of matrix components during fibrosis and/or indirectly by influencing the behaviour of neighbouring cell types. In particular, it is now well recognized that fibroblasts and their secreted products are crucial in tumour development and the progression of inflammatory diseases [3-7]. 1.3. Not all fibroblasts are the same Fibroblasts are Tebanicline hydrochloride a diverse cell type and display clear topographic differentiation and positional memory that is transcriptionally imprinted [8,9]. Despite this heterogeneity there are very few selective markers that allow clear discrimination between fibroblast subtypes. What is known is usually that fibroblasts are extremely versatile connective tissue cells and display a remarkable capacity to differentiate into other members of the connective tissue family including cartilage, bone, adipocyte, and easy muscle cells. Further, not all fibroblasts are mesodermal in origin. For example, fibroblasts in the head and neck region are derived from the neural crest (ectoderm). Even within a single tissue there is growing evidence that fibroblasts are not a homogeneous populace, but exist as subsets of cells, much like tissue macrophages and dendritic cells [10,11], It is Mouse monoclonal to CK1 likely that connective tissue contains a mixture of distinct fibroblast lineages with mature fibroblasts existing side by side with immature fibroblasts (often called mesenchymal fibroblasts) that are capable of differentiating into other connective tissue cells. Tantalizing evidence now suggests that as is the case for endothelial cells, fibroblast precursors (termed fibrocytes) circulate in peripheral blood. These cells share many properties of bone marrow stromal stem cells and are capable of differentiating into several cell lineages. This diversity in phenotype and function that characterizes fibroblasts from different anatomical sites may play a significant role in the intrinsic susceptibility of different organs to inflammatory insults. It may also provide the molecular basis for the well described but as yet poorly understood clinical finding that relapses in chronic inflammation are often tissue and site specific. Furthermore, recent studies have shown that thymic fibroblasts play an important role in early T cell development, providing a molecular explanation for long standing observations that destruction of the cephalic neural crest results in retarded lymphoid development in the thymus, as well as producing craniofacial and cardiac defects . A critical advance to this field will be to identify and characterize fibroblast subsets, and to determine the relative contribution of these different subsets to tissue homeostasis and disease progression in diseases such as chronic inflammation and cancer. Therefore, the aims of the stromal cell section in HLDA 8 were: Identify fibroblast specific antibodies (or at least those with expression mainly limited to fibroblasts). Identify antibodies that can discriminate between fibroblasts from different sites. Identify antibodies that can discriminate between normal tissue fibroblasts from one site and diseased tissue (fibroblasts) from the same site. 2. Methods Antibodies were solicited from scientists in the field as well as open recruitment during the period January 2001 to June 2004. This resulted in 62 potential antibodies being assigned to the HLDA8 stromal cell section. These 62 antibodies were screened by immunohistochemistry of frozen sections of tonsil, synovium, liver, and skin as well as by.