Engineered regulatory T (T) cells have emerged as precision therapeutics aimed at inducing immune tolerance while reducing the risks associated with generalized immunosuppression. This Viewpoint highlights the opportunities and challenges for engineered T cell therapies in treating autoimmune and other inflammatory diseases.
View Article and Find Full Text PDFIt has previously been reported that VEGF-A stimulates megakaryocyte (MK) maturation in vitro. Here we show that treatment of mice with the isoform VEGF-A(165) resulted in a significant increase in circulating numbers of platelets. Using specific VEGFR1 and VEGFR2 blocking mAbs and selective VEGFR1 and 2 agonists, PlGF-2 and VEGF-E, respectively, we show directly that stimulation of VEGFR1, but not VEGFR2, increases circulating platelet numbers in vivo.
View Article and Find Full Text PDFMesenchymal stem cells (MSCs) were discovered as a rare population of non-hematopoietic stem cells that reside in the bone marrow and interact closely with hematopoietic stem cells to support their growth and differentiation. MSCs are multipotent cells that have the ability to differentiate into cells of the mesenchymal lineage including adipocytes, osteocytes and chondrocytes and they have been reported to home to areas of tissue injury and participate in tissue repair. More recently, MSCs have also been described to possess anti-inflammatory and immunomodulatory properties that can affect multiple arms of the immune system.
View Article and Find Full Text PDFThe last decade has seen a dramatic rise in the development of new cellular therapeutics in a wide range of indications. There have been acceptable safety profiles reported in early studies using blood-derived and adherent stem cell products, but also an inconsistent efficacy record. Further expansion has been hindered in part by a lack of capital (both private and public) and delayed entry into the cell therapy space by large healthcare and pharmaceutical companies, those members of the industry most reliably able to initiate and maintain advanced-phase clinical trials.
View Article and Find Full Text PDFAdult human bone marrow-derived stem cells, having the ability to differentiate into cells of multiple lineages, have been isolated and propagated by varied protocols, including positive (CD105(+))/negative (CD45(-)GlyA(-)) selection with immunomagnetic beads, or direct plating into selective culture media. Each substratum-adherent cell population was subjected to a systematic analysis of their cell surface markers and differentiation potential. In the initial stages of culture, each cell population proliferated slowly, reaching confluence in 10-14 days.
View Article and Find Full Text PDFCCAAT/enhancer binding proteins (C/EBPs) are a family of factors that regulate cell growth and differentiation. These factors, particularly C/EBPalpha and C/EBPepsilon, have important roles in normal myelopoiesis. In addition, loss of C/EBP activity appears to have a role in the pathogenesis of myeloid disorders including acute myeloid leukemia (AML).
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