Acute Esophageal Necrosis Following Acetaminophen Overdose: An Unreported Cause of Black Esophagus.

Description Acute esophageal necrosis (AEN), also known as "black esophagus" or Gurvits syndrome, is an uncommon finding with an unclear etiology and pathogenesis. This condition often presents as an upper gastrointestinal bleed in older men with multiple comorbidities. AEN is characterized by circumferential black, necrotic mucosa in the esophagus. We present a case of AEN following acetaminophen overdose. The patient was ultimately discharged from the hospital with oral omeprazole twice daily, a clear liquid diet, and a recommendation for follow-up in the outpatient setting for repeat EGD in 4 to 6 weeks. Acetaminophen overdose, although a rare cause, must be considered as a possible etiology of AEN.

Fetal stem cells from extra-embryonic tissues: do not discard.

Stem cells hold promise to treat diseases currently unapproachable, including Parkinson's disease, liver disease and diabetes. Seminal research has demonstrated the ability of embryonic and adult stem cells to differentiate into clinically useful cell types in vitro and in vivo. More recently, the potential of fetal stem cells derived from extra-embryonic tissues has been investigated. Fetal stem cells are particularly appealing for clinical applications. The cells are readily isolated from tissues normally discarded at birth, avoiding ethical concerns that plague the isolation embryonic stem cells. Extra-embryonic tissues are large, potentially increasing the number of stem cells that can be extracted. Lastly, the generation and sequestration of cells that form extra-embryonic tissues occurs early in development and may endow resident stem cell populations with enhanced potency. In this review we summarize recent work examining the plasticity and clinical potential of fetal stem cells isolated from extra-embryonic tissues.

Isolation, characterization, and differentiation of stem cells derived from the rat amniotic membrane.

Stem-cell-based therapies may offer treatments for a variety of intractable diseases. A fundamental goal in stem-cell biology concerns the characterization of diverse populations that exhibit different potentials, growth capabilities, and therapeutic utilities. We report the characterization of a stem-cell population isolated from tissue explants of rat amniotic membrane. Similar to mesenchymal stem cells, these amnion-derived stem cells (ADSCs) express the surface markers CD29 and CD90, but were negative for the lymphohematopoietic markers CD45 and CD11b. ADSCs exist in culture in a multidifferentiated state, expressing neuroectodermal (neurofilament-M), mesodermal (fibronectin), and endodermal (alpha-1-antitrypsin) genes. To assess plasticity, ADSCs were subjected to a number of culture conditions intended to encourage differentiation into neuroectodermal, mesodermal, and endodermal cell types. ADSCs cultured in a defined neural induction media assumed neuronal morphologies and up-regulated neural-specific genes. Under different conditions, ADSCs were capable of differentiating into presumptive bone and fat cells, indicated by the deposition of mineralized matrix and accumulated lipid droplets, respectively. Moreover, ADSCs cultured in media that promotes liver cell differentiation up-regulated liver-specific genes (albumin) and internalized low-density lipoprotein (LDL), consistent with a hepatocyte phenotype. To determine whether this observed plasticity reflects the presence of true stem cells within the population, we have derived individual clones from single cells. Clonal lines recapitulate the expression pattern of parental ADSC cultures and are multipotent. ADSCs have been cultured for 20 passages without losing their plasticity, suggesting long-term self-renewal. In sum, our data suggest that ADSCs and derived clonal lines are capable of long-term self-renewal and multidifferentiation, fulfilling all the criteria of a stem-cell population.

Disparate host response and donor survival after the transplantation of mesenchymal or neuroectodermal cells to the intact rodent brain.

BACKGROUND: To circumvent ethical and legal complications associated with embryonic cell sources, investigators have proposed the use of nonneural donor sources for use in neural transplantation strategies. Leading candidate sources include autologous marrow stromal cells (MSCs) and fibroblasts, which are mesodermal derivatives. However, we recently reported that MSCs transplanted to the adult brain are rapidly rejected by an inflammatory response. Whether extrinsic variables or intrinsic mesenchymal traits stimulated inflammation and rejection is unknown. To determine the future utility of these cells in neural transplantation, we have now performed a systematic analysis of MSC transplantation to the brain. METHODS: To examine the effects of extrinsic variables on transplantation, green fluorescent protein (GFP)-expressing rat MSCs, cultured under distinct conditions, were transplanted stereotactically to the normal adult rat striatum, and donor survival and the host response was compared. To examine whether intrinsic donor traits promoted rejection, 50,000 GFP-expressing rat MSCs, fibroblasts, or astrocytes were transplanted stereotactically to the adult rat striatum and graft survival and the host response was compared. RESULTS: Irrespective of preoperative culture conditions, MSCs elicited an inflammatory response and were rejected by 14 days, indicating acute rejection was not mediated by culture conditions. Comparison of MSC, fibroblast, or astrocyte grafts revealed that mesenchymal derivatives, MSCs and fibroblasts, elicited an inflammatory response and were rapidly rejected, whereas neuroectodermal astrocytes demonstrated robust survival in the absence of inflammation. CONCLUSIONS: Our findings suggest that intrinsic characteristics of mesenchymal cells may stimulate host inflammation, and thus may not represent an ideal donor source for transplantation to the adult brain.

Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia.

Abstract The remarkable plasticity of marrow stromal cells (MSCs) after transplantation to models of neurological disease and injury has been described. In this report, we investigated the plasticity and long-term survival of MSCs transplanted into the normal brain. MSCs were isolated from green fluorescent protein (GFP) transgenic rats and double-labeled with 5-bromo-2-deoxyuridine (BrdU) and bis benzamide (BBZ) prior to transplantation into the adult hippocampus or striatum. Surgery elicited an immediate inflammatory response. MSC grafts were massively infiltrated by ED1-positive microglia/macrophages and surrounded by a marked astrogliosis. By 14 days, graft volume had retracted and GFP immunoreactivity was absent, indicating complete donor rejection. Consequently, MSCs did not exhibit plasticity formerly identified in other studies. However, BrdU- and BBZ-labeled cells were detected up to 12 weeks. Control transplants of nonviable MSCs demonstrated the transfer of donor labels to host cells. Unexpectedly, BrdU labeling was colocalized to host phagocytes, astrocytes, and neurons in both regions. Our results indicate that MSCs transplanted to the intact adult brain are rejected by an inflammatory response. Moreover, use of the traditional cell labels BrdU and BBZ may provide a misleading index of donor survival and differentiation after transplantation.

Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival.

We recently differentiated adult rat and human bone marrow stromal cells (MSCs) into presumptive neurons in cell culture. To determine whether the MSCs assume neuronal functions in vivo, we now characterize for the first time engraftment, migration, phenotypic expression, and long-term survival after infusion into embryonic day 15.5 (E15.5) rat ventricles in utero. By E17.5, donor cells formed discrete spheres in periventricular germinal zones, suggesting preferential sites of engraftment. The cells expressed progenitor vimentin and nestin but not mature neuronal markers. By E19.5, a subset assumed elongated migratory morphologies apposed to radial nestin-positive fibers running through the cortical white matter and plate, suggesting migration along radial glial processes. Cells remaining in germinal zones extended long, vimentin-positive fibers into the parenchyma, suggesting that the MSCs generated both migratory neurons and guiding radial glia. Consistent with this suggestion, >50% of cultured mouse MSCs expressed the neuroprecursor/radial glial protein RC2. From E19.5 to postnatal day 3, MSCs populated distant areas, including the neocortices, hippocampi, rostral migratory stream, and olfactory bulbs. Whereas donor cells confined to the subventricular zone continued to express nestin, cells in the neocortex and midbrain expressed mature neuronal markers. The donor cells survived for at least 2 months postnatally, the longest time examined. Confocal analysis revealed survival of thousands of cells per cubic millimeter in the frontal cortex and olfactory bulb at 1 month. In the cortex and bulb, 98.6 and 77.3% were NeuN (neuronal-specific nuclear protein) positive, respectively. Our observations suggest that transplanted adult MSCs differentiate in a regionally and temporally specific manner.