Cells Of Embryonic Origin Research Articles

Nephrogenic Adenoma of the Urinary Bladder after Kidney Transplantation: Long-Term Follow-Up

Nephrogenic adenoma is a rare lesion that consists of epithelial cells arranged in tubular form, resembling tubules in the renal medulla, and is found usually in the urinary bladder although it can occur anywhere in the transitional epithelium of the lower urinary tract. The first case of nephrogenic adenoma of the urinary bladder was reported before the first kidney transplantation, and the lesion has been reported in patients with and without renal transplantation. The origin of cells in nephrogenic adenoma is debated and has been postulated to arise from cells of embryonic origin or from metaplasia secondary to chronic irritation or from implantation of allograft cells in patients with kidney transplantation. The long-term outcome and potential to convert into malignancy are not established, and therefore, there are no recommendations on how to follow up these patients. We present a case of a patient who was found to have nephrogenic adenoma of the urinary bladder during his second kidney transplantation from a cadaveric donor. He had undergone living donor kidney transplantation previously which subsequently failed. The patient did not manifest any symptoms of nephrogenic adenoma. During a follow-up period of 5 years, he has not manifested any symptoms related to nephrogenic metaplasia. Histopathological examination 5 years after the second transplantation did not show any malignant change. It can be concluded that nephrogenic adenoma is likely to behave in benign fashion post kidney transplantation.

Trophoblasts promote induction of a regulatory phenotype in B cells that can protect against detrimental T cell-mediated inflammation.

A successful outcome to pregnancy is critically dependent on the initiation of maternal immune tolerance before embryo implantation. Cells of embryonic origin that come in contact with the uterine microenvironment can exert influence over the phenotype and function of immune cells to facilitate robust implantation; however, what influence they may have on B cells remains unknown. In this study, we investigate the effect of human trophoblast cells on B-cell phenotype and the subsequent effect on peri-implantation events. We cultured purified human B cells with the first-trimester human trophoblast cell line Swan 71 to investigate trophoblast-B-cell interactions and utilized trophoblast spheroids in an in vitro implantation model of migration and invasion. Trophoblast-educated B cells or TE-B cells were found to consist of B cells in committed lineages such as plasmablasts and memory B cells, as well as increased proportions in subsets of CD24hi CD27+ regulatory B cells and CD19+ IL-10+ B cells. Conditioned media from the TE-B cells showed reduced production of pro-inflammatory cytokines that influenced the T-cell proliferation and cytokine production. Using trophoblast spheroids, we assessed the role of TE-B cells in trophoblast invasion and migration. Our results demonstrate a protective effect of TE-B-conditioned media against deleterious inflammation as evidenced by survival of the trophoblast spheroid in the presence of an immune assault and promotion of a migratory phenotype. We posit that trophoblast-mediated education of B cells leads to their acquisition of properties capable of modulating inflammation in the uterine environment during the peri-implantation period.

The large fraction of heterochromatin in Drosophila neurons is bound by both B-type lamin and HP1a

BackgroundIn most mammalian cell lines, chromatin located at the nuclear periphery is represented by condensed heterochromatin, as evidenced by microscopy observations and DamID mapping of lamina-associated domains (LADs) enriched in dimethylated Lys9 of histone H3 (H3K9me2). However, in Kc167 cell culture, the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with the domains of heterochromatin protein 1a (HP1a).ResultsHere, using cell type-specific DamID we mapped genome-wide LADs, HP1a and Polycomb (Pc) domains from the central brain, Repo-positive glia, Elav-positive neurons and the fat body of Drosophila third instar larvae. Strikingly, contrary to Kc167 cells of embryonic origin, in neurons and, to a lesser extent, in glia and the fat body, HP1a domains appear to overlap strongly with LADs in both the chromosome arms and pericentromeric regions. Accordingly, centromeres reside closer to the nuclear lamina in neurons than in Kc167 cells. As expected, active gene promoters are mostly not present in LADs, HP1a and Pc domains. These domains are occupied by silent or weakly expressed genes with genes residing in the HP1a-bound LADs expressed at the lowest level.ConclusionsIn various differentiated Drosophila cell types, we discovered the existence of peripheral heterochromatin, similar to that observed in mammals. Our findings support the model that peripheral heterochromatin matures enhancing the repression of unwanted genes as cells terminally differentiate.

Functional significance of CD105-positive cells in papillary renal cell carcinoma

BackgroundCD105 was postulated as a renal cell carcinoma (RCC) stem cell marker, and CD133 as a putative RCC progenitor. Hypoxia, a natural microenvironment that prevails in tumors, was also incorporated into the study, especially in terms of the promotion of hypothetical stem-like cell properties.MethodsWithin this study, we verify the existence of CD105+ and CD133+ populations in selected papillary subtype RCC (pRCC) cell lines. Both populations were analyzed for correlation with stem-like cell properties, such as stemness gene expression, and sphere and colony formation. For the preliminary analysis, several RCC cell lines were chosen (786-O, SMKT-R2, Caki-2, 796-P, ACHN, RCC6) and the control was human kidney cancer stem cells (HKCSC) and renal cells of embryonic origin (ASE-5063). Four cell lines were chosen for further investigation: Caki-2 (one of the highest numbers of CD105+ cells; primary origin), ACHN (a low number of CD105+ cells; metastatic origin), HKCSC (putative positive control), and ASE-5063 (additional control).ResultsIn 769-P and RCC6, we could not detect a CD105+ population. Hypoxia variously affects pRCC cell growth, and mainly diminishes the stem-like properties of cells. Furthermore, we could not observe the correlation of CD105 and/or CD133 expression with the enhancement of stem-like properties.ConclusionsBased on this analysis, CD105/CD133 cannot be validated as cancer stem cell markers of pRCC cell lines.

The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes

Genome stability relies on epigenetic mechanisms that enforce repression of endogenous retroviruses (ERVs). Current evidence suggests that distinct chromatin-based mechanisms repress ERVs in cells of embryonic origin (histone methylation dominant) vs. more differentiated cells (DNA methylation dominant). However, the latter aspect of this model has not been tested. Remarkably, and in contrast to the prevailing model, we find that repressive histone methylation catalyzed by the enzyme SETDB1 is critical for suppression of specific ERV families and exogenous retroviruses in committed B-lineage cells from adult mice. The profile of ERV activation in SETDB1-deficient B cells is distinct from that observed in corresponding embryonic tissues, despite the loss of repressive chromatin modifications at all ERVs. We provide evidence that, on loss of SETDB1, ERVs are activated in a lineage-specific manner depending on the set of transcription factors available to target proviral regulatory elements. These findings have important implications for genome stability in somatic cells, as well as the interface between epigenetic repression and viral latency.

Stem Cells Derived from Human Amniotic Fluid Contribute to Acute Kidney Injury Recovery

Stem cells isolated from human amniotic fluid are gaining attention with regard to their therapeutic potential. In this work, we investigated whether these cells contribute to tubular regeneration after experimental acute kidney injury. Cells expressing stem cell markers with multidifferentiative potential were isolated from human amniotic fluid. The regenerative potential of human amniotic fluid stem cells was compared with that of bone marrow-derived human mesenchymal stem cells. We found that the intravenous injection of 3.5 × 10(5) human amniotic fluid stem cells into nonimmune-competent mice with glycerol-induced acute kidney injury was followed by rapid normalization of renal function compared with injection of mesenchymal stem cells. Both stem cell types showed enhanced tubular cell proliferation and reduced apoptosis. Mesenchymal stem cells were more efficient in inducing proliferation than amniotic fluid-derived stem cells, which, in contrast, were more antiapoptotic. Both cell types were found to accumulate within the peritubular capillaries and the interstitium, but amniotic fluid stem cells were more persistent than mesenchymal stem cells. In vitro experiments demonstrated that the two cell types produced different cytokines and growth factors, suggesting that a combination of different mediators is involved in their biological actions. These results suggest that the amniotic fluid-derived stem cells may improve renal regeneration in acute kidney injury, but they are not more effective than mesenchymal stem cells.

Multipotent Progenitor Cells in Regenerative Cardiovascular Medicine

Regenerative therapies for heart diseases require the understanding of the molecular mechanisms that govern the fates and differentiation of the diverse muscle and nonmuscle cell lineages that form during heart development. During mouse cardiogenesis, the major lineages of the mature heart, cardiomyocytes, smooth muscle, endothelial cells, and cardiac mesenchyme, arise from multipotent cardiovascular progenitors expressing the transcription factors Mesp1, Isl1, Nkx2-5, and Tbx18. Recent identification of stem/progenitor cells of embryonic origin with intrinsic competence to differentiate into multiple lineages of the heart offers exciting new possibilities for cardiac regeneration. When combined with new advances in nuclear reprogramming, the prospect of achieving autologous, cardiomyogenic, stem-cell-based therapy might be within reach.

Systemic Neurotransplantation - A Problem-Oriented Systematic Review

Systemic neurotransplantation (SNT) was introduced in the laboratory in 2000 and currently it is being widely examined in animal models of neurological disorders. The aim of this systematic review was to evaluate the current state of knowledge in the field of experimental SNT and the premise for the introduction of clinical trials. PubMed was searched and 60 articles utilizing an SNT approach were found and subjected to analysis. The time window for cell transplantation was addressed in only two studies, with contradictory results. Immunosuppression was applied in 25% of studies. No study addressed the justification for immunosuppression. Bone marrow was the most frequent source of grafted cells, followed by cord blood and then by cells of embryonic origin. Studies investigating dose-dependency revealed no satisfactory results with transplantation of less than 10(6) cells/animal; the efficient dose most frequently ranged from 10(6)-10(7) cells/animal (mice and rats). The behavioral effects of cell transplantation were assessed in 75% of all studies; significant improvement was achieved in 95% of them. Morphological effect was evaluated in half of the studies; significant positive effect was achieved in 73% of them. Experimental attempts to elucidate the mechanisms mediating cell-dependent effect were not undertaken in half of the studies. In the other half, the most frequent mechanisms were growth factors, neurogenesis and immunomodulation. SNT still seems to be at the very initial stage of development. Many critical factors have not been sufficiently addressed in laboratory studies and they must be clarified before the introduction of clinical trials.

Isolation of a new mouse 3beta-hydroxysteroid dehydrogenase isoform, 3beta-HSD VI, expressed during early pregnancy.

The enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD) is a key enzyme in the biosynthesis of steroid hormones. To date, this laboratory has isolated and characterized five distinct 3beta-HSD complementary DNAs (cDNAs) in the mouse (3beta-HSD I through V). These different forms are expressed in a tissue- and developmentally-specific manner and fall into two functionally distinct enzymes. 3beta-HSD I and III, and most likely II, function as dehydrogenase/isomerases, whereas 3beta-HSD IV and V function as 3-ketosteroid reductases. This study describes the isolation, characterization, and tissue-specific expression of a sixth member of this gene family, 3beta-HSD VI. This new isoform functions as an NAD+-dependent dehydrogenase/isomerase exhibiting very low Michaelis-Menten constant (Km) values for pregnenolone (approximately 0.035 microM) and dehydroepiandrosterone (approximately 0.12 microM). 3beta-HSD VI is the earliest isoform to be expressed during embryogenesis in cells of embryonic origin at 7 and 9.5 days postcoitum (pc), and is the major isoform expressed in uterine tissue at the time of implantation (4.5 days pc) and continues to be expressed in uterine tissue at 6.5, 7.5, and 9.5 days pc. 3beta-HSD VI is expressed in giant trophoblasts at 9.5 days pc and is expressed in the placenta through day 15.5 pc. In the adult mouse, 3beta-HSD VI appears to be the only isoform expressed in the skin and also is expressed in the testis, but to a lesser extent than 3beta-HSD I. Mouse 3beta-HSD VI cDNA is orthologous to human 3beta-HSD I cDNA. Human type I 3beta-HSD has been shown to be the only isoform expressed in the placenta and skin. The demonstration that mouse 3beta-HSD VI functions as a dehydrogenase/isomerase and is the predominant isoform expressed during the first half of pregnancy in uterine tissue and in embryonic cells suggests that this isoform may be involved in local production of progesterone, which is needed for successful implantation of the blastocyst and/or maintenance of early pregnancy.

Infection of bovine cells of embryonic origin by amphotropic retroviral vectors.

Two amphotropic-based mouse retroviral vectors carrying the neomycin-resistance gene were used to infect four bovine cell lines. Two cell lines, bovine kidney and spleen cells, were refractory to the infection while two independent bovine cells of apparent embryonic origin were infected by the amphotropic retroviral vectors at a measurable titer. Southern blot analysis reveals the presence of neomycin-resistance gene in the G418-resistant bovine cells. The results demonstrate the successful transfer of a gene to bovine cells of embryonic origin using a murine retroviral vector system.

Natural killer lymphocyte activity against cells of embryonic origin

Natural killer lymphocyte activity against cells of embryonic origin

Detection of B-tropic endogenous type-C virus in viral isolates originating from induced BALB/K-3T3 cells.

Isoelectric focusing (IEF) analysis of class I endogenous type-C virus induced by iododeoxyuridine treatment of BALB/K-3T3 cells revealed, in addition to the major variant of the p30 polypeptide, which has an isoelectric point of 6.1 (pI 6.1 isop30), a minor isop30 with a pI of 5.6. This value was also found for a prototype BALB/c B-tropic endogenous virus isolate. The pI 5.6 isop30 of the N-tropic isolate was amplified by long-term virus replication in B-type mouse cells, and comparative IEF and XC-assay data suggest that it may correspond to a B-tropic subpopulation which has not yet been detected in vitro in mouse cells of embryonic origin.