Transplantation

About: Transplantation is a research topic. Over the lifetime, 276584 publications have been published within this topic receiving 7961661 citations.

Alginate hydrogels as biomaterials.

Abstract: [Image: see text] Alginate hydrogels are proving to have a wide applicability as biomaterials. They have been used as scaffolds for tissue engineering, as delivery vehicles for drugs, and as model extracellular matrices for basic biological studies. These applications require tight control of a number of material properties including mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules. Control over these properties can be achieved by chemical or physical modifications of the polysaccharide itself or the gels formed from alginate. The utility of these modified alginate gels as biomaterials has been demonstrated in a number of in vitro and in vivo studies.Micro-CT images of bone-like constructs that result from transplantation of osteoblasts on gels that degrade over a time frame of several months leading to improved bone formation.

Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin

Abstract: It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell-like state by introducing combinations of four transcription factors. However, the therapeutic potential of such induced pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell anemia mouse model, we show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. Our results provide proof of principle for using transcription factor-induced reprogramming combined with gene and cell therapy for disease treatment in mice. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy.

Stromal gene expression predicts clinical outcome in breast cancer

Abstract: Although it is increasingly evident that cancer is influenced by signals emanating from tumor stroma, little is known regarding how changes in stromal gene expression affect epithelial tumor progression. We used laser capture microdissection to compare gene expression profiles of tumor stroma from 53 primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumor-derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node-negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.

Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant.

Abstract: Multiple myeloma (MM) is a malignant plasma cell disorder accounting for about 10% of haematological malignancies. The disease is characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin heavy and/or light chain (paraprotein, M-protein or Mcomponent). This patient-specific paraprotein is present in the serum and/or urine of all patients except in the 1–2% of patients with non-secretory myeloma. Typical clinical and laboratory features in patients with MM include bone pain (due to lytic lesions or osteoporosis), anaemia, renal insufficiency, hypercalcaemia, increased susceptibility to infection and constitutional symptoms resulting in poor performance status. Less common complications include cord compression due to extramedullary plasmacytomas or vertebral collapse, peripheral neuropathy, amyloidosis and hyperviscosity syndrome (Malpas, 1998). Prior to the introduction of alkylating agents, the median survival of patients with MM was less than a year (Korst et al, 1964; Holland et al, 1966). Approximately 60% of patients respond to initial treatment with conventional chemotherapy, but although survival is prolonged by treatment the median survival remains approximately 3 years (Bergsagel, 1998). Complete remissions are rare and all patients ultimately relapse, resulting in c 25% survival at 5 years and <10% survival at 10 years. Criteria by which different treatment regimens can be evaluated include the proportion of patients achieving an objective response, the duration of response, and survival. Over the past 10–15 years high-dose therapy followed by haemopoietic stem-cell rescue, either allogeneic or autologous, has been increasingly employed in the treatment of multiple myeloma. For a number of reasons the existing criteria for the assessment of disease response have not proved entirely satisfactory for the analysis of disease outcome after high-dose therapy. In particular, there has been no generally agreed definition of complete response. Agreed definitions of response and progression are essential to ensure consistency of reporting within the transplant registries and to enable comparison of results from different studies and/or different treatment centres. New criteria for response and progression have therefore been developed as a result of discussions between representatives of the Myeloma Subcommittee of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) and representatives of the Myeloma Working Committee of the Autologous Blood and Marrow Transplant Registry (ABMTR) and the International Bone Marrow Transplant Registry (IBMTR). These criteria will now form the working definitions of response and progression for the purposes of data collection and registry-based studies. Currently none of the registries include specific diagnostic criteria, although all record the relevant investigations performed at diagnosis. However, we wish to emphasize that all patients undergoing high-dose therapy should have proven myeloma which requires treatment. At present highdose therapy is not recommended for patients with equivocal myeloma or those with stage I disease. We have not at this stage reviewed the criteria for the diagnosis of myeloma, but there may be a requirement for this in the future. For example, because of the increasing use of high-dose therapy for the treatment of primary amyloidosis, it will be important to establish clear guidelines for the differential diagnosis between this condition and multiple myeloma with amyloid.