Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium. The homogenous layer of adherent cells exhibited a typical fibroblast-like morphology, a large expansive potential, and cell cycle characteristics including a subset of quiescent cells. In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic, osteogenic and chondrogenic lineages. Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells, which uniformly expressed CD29, CD44, CD73, CD105, CD166, laminin, fibronectin and vimentin while being negative for expression of CD31, CD34, CD45 and alpha-smooth muscle actin. Most importantly, immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-I), but they did not express MHC-II molecules. Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli. This strongly implies that they may have potential application in allograft transplantation. Since placenta and UCB are homogeneous, the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.
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PMID:Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation. 1604 17

The immunosuppressive drug mycophenolate mofetil (MMF) is used to prevent organ rejection after transplantation and has shown some efficacy to prevent the fibrotic complications that occur during autoimmune diseases such as systemic sclerosis or during graft-versus-host disease (GVHD). We tested the hypothesis that MMF may exert direct effects on fibroblast extracellular matrix remodeling. Incubation of human lung fibroblast cultures with MMF led to dose- and time-dependent reduction in the synthesis and expression of type I collagen. Inhibition of COL1A1 and COL1A2 mRNA steady-state levels occurred at the level of transcription via repression of their promoters. In contrast, MMF significantly enhanced the expression and the synthesis of interstitial collagenase (matrix metalloproteinase-1). MMF was also found to diminish the capacity of fibroblast to contract mechanically unloaded collagen lattices and to reduce the synthesis of alpha-smooth muscle actin, a marker of the contractile myofibroblast phenotype. In addition, MMF diminished the fibroblasts motility. In conclusion, we provide novel mechanism by which MMF alters fibroblast functions important for wound healing and implicated in the development of tissue fibrosis, e.g., collagen production, extracellular matrix contraction, and cell migration. Such properties may contribute to the beneficial therapeutic effects of MMF against fibrotic lesions developing in systemic sclerosis or during GVHD.
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PMID:In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil. 1727 76