isolation-and-analysis-of-hematopoietic-stem-cells-from-the-placenta

Isolation and Analysis of Hematopoietic Stem Cells from the Placenta

Hematopoietic stem cells (HSCs) have the ability to self-renew and generate all cell types of the blood lineages throughout the lifetime of an individual. ...

Anatomische Variation der Koexistenz der 4. und 5. kurze Metacarpus Knochen, sesamoid Geh&ouml;rkn&ouml;chelchen und Exostosen der Ulna und Radius in einer Hand: ein Fallbericht.

Anatomical variation of co-existence of 4th and 5th short metacarpal bones, sesamoid ossicles and exostoses of ulna and radius in the same hand: a case report.

The basic helix-loop-helix transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Scl(fl/fl) fetal liver progenitor cell lines. Analysis of Mef2C(-/-) embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre(+)Mef2C(fl/fl) mice exhibited platelet defects similar to those observed in Scl-deficient mice. The platelet counts were reduced, whereas platelet size was increased and the platelet shape and granularity were altered. Furthermore, megakaryopoiesis was severely impaired in vitro. Chromatin immunoprecipitation microarray hybridization analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl-independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B-cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages.

Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis.

Das grundlegende Helix-Schleife-Helix-Transkription Faktor Stammzellen Leuk&auml;mie-gen (Scl) ist ein master Regulator f&uuml;r die Blutbildung unverzichtbar f&uuml;r h&auml;matopoetische Spezifikation und richtige Differenzierung der sogenannten Erythroid und Megakaryozyt. Die kritischen nachgelagerte Ziele des Scl bleiben jedoch nicht definiert. Hier haben wir einen Roman Scl-Ziel-gen, Faktor Muskelfaser Vergr&ouml;&szlig;erer &Uuml;bertragungfaktor 2C (Mef2C) aus Scl(fl/fl) fetalen Leber Stammvater Zelllinien identifiziert. Analyse von Mef2C(-/-) Embryonen zeigte, dass Mef2C, im Gegensatz zu Scl, f&uuml;r Spezifikation in primitiven oder endg&uuml;ltiger h&auml;matopoetischen Linien nicht wichtig. Jedoch stellte Erwachsene VavCre(+)Mef2C(fl/fl) M&auml;use Thrombozyten M&auml;ngel Scl-defizienten M&auml;usen &auml;hnlich. Die Thrombozyten-Grafen wurden reduziert, w&auml;hrend die Thrombozyten vergr&ouml;&szlig;ert wurde und die Thrombozyten Form und Granularit&auml;t wurden ver&auml;ndert. Dar&uuml;ber hinaus wurde die Megakaryopoiesis stark in-vitro-beeintr&auml;chtigt. Chromatin Immunopr&auml;zipitation Microarray-Hybridisierung-Analyse ergab, dass Mef2C direkt von Scl in megakaryocytic Zellen, aber nicht in Erythroid Zellen reguliert wird. Dar&uuml;ber hinaus wurde eine Scl-unabh&auml;ngige Voraussetzung f&uuml;r Mef2C in B-lymphatischen Hom&ouml;ostase Mef2C-defizienten M&auml;usen, gekennzeichnet als starker altersbedingt Reduktion von bestimmten B-Zellen Vorl&auml;uferzellen Populationen erinnert an vorzeitiger Alterung beobachtet. Zusammenfassend l&auml;sst sich sagen identifiziert diese Arbeit Mef2C als integraler Mitglied der h&auml;matopoetischen Transkriptionsfaktoren mit unterschiedlichen upstream Regulierungsmechanismen und funktionale Anforderungen in Megakaryozyt und B-lymphatischen &Uuml;bertragungslinien.

Mef2C ist eine &Uuml;bertragungslinie eingeschr&auml;nkten Ziel Scl/Tal1 und reguliert Megakaryopoiesis und B-Zell-Hom&ouml;ostase.

The stem-cell leukemia gene (SCL/tal1) is essential for the formation of all blood lineages. SCL is first expressed in mesodermal cells that give rise to embryonic blood cells, and continues to be expressed in fetal and adult hematopoietic stem cells (HSCs). However, SCL is not required for the maintenance of established long-term repopulating (LTR) HSCs in the adult. The time point at which HSC development becomes SCL independent has not been defined. Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (Tie2) expression appears in hemogenic and vasculogenic sites shortly after SCL. We therefore used the Tie2Cre mouse to inactivate SCL early during embryonic and fetal hematopoiesis. Tie2Cre completely inactivated SCL in yolk sac, the aortagonad-mesonephros (AGM) region, and fetal liver hematopoietic cells and circulating blood cells. However, the fetal liver was colonized by functional LTR-HSCs. Yet SCL remained crucial for proper differentiation of both primitive and definitive red cells and megakaryocytes. These results indicate that the SCL-dependent phase of HSC development ends before Tie2Cre-mediated gene ablation becomes effective.

Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development.

Tie2Cre-vermittelte Gen-Ablation definiert den Stamm-Zell-Leuk&#xE4;mie-Gen (SCL/tal1)-abh&#xE4;ngigen Fenster w&#xE4;hrend der h&#xE4;matopoetischen Stamm-Zell-Entwicklung.

The hematopoietic system develops during embryogenesis at temporally and anatomically restricted sites. The anatomical origin of definitive HSCs is not fully resolved, and little is known about how the different fetal hematopoietic microenvironments direct HSC development. Here, we show that the mouse placenta functions as a hematopoietic organ that harbors a large pool of pluripotent HSCs during midgestation. The onset of HSC activity in the placenta parallels that of the AGM (aorta-gonad-mesonephros) region starting at E10.5-E11.0. However, the placental HSC pool expands until E12.5-E13.5 and contains >15-fold more HSCs than the AGM. The expansion of the CD34(+)c-kit(+) HSC pool in the placenta occurs prior to and during the initial expansion of HSCs in the fetal liver. Importantly, the placental HSC pool is not explained by rare circulating HSCs, which appear later. These data support an important, but unappreciated, role for the placenta in establishing the mammalian definitive hematopoietic system.

The placenta is a niche for hematopoietic stem cells.

Die Plazenta ist eine Nische f&#xFC;r blutbildende Stammzellen.

The Wilms tumor gene 1 (WT1) encodes a zinc-finger-containing transcription factor highly expressed in immature hematopoietic progenitor cells. Overexpression and presence of somatic mutations in acute leukemia indicate a role for WT1 in the pathogenesis of leukemia. CD34+ progenitor cells were transduced with one splice variant of human WT1 without the KTS insert in the zinc-finger domain, WT1(+/-), and with a deleted mutant of WT1 lacking the entire zinc-finger region, WT1(delZ), thus incapable of binding DNA. We show that inhibition of erythroid colony formation and differentiation is absolutely dependent on the DNA-binding zinc-finger domain of WT1. Unexpectedly, however, WT1(delZ) was equally effective as wild type protein in the reduction of myeloid clonogenic growth as well as in stimulation of myeloid differentiation, as judged by the expression of cell surface CD11b. Expression of neither WT1(+/-) nor WT1(delZ) upregulated mRNA for the cdk inhibitor p21(Waf1/Cip1) or p27Kip1. Our results demonstrate that WT1 affects proliferation and differentiation in erythroid and myeloid cells by different molecular mechanisms, and suggest that mutations affecting the zinc-finger domain of WT1 could interfere with normal differentiation in the pathogenesis of leukemia.

DNA-binding dependent and independent functions of WT1 protein during human hematopoiesis.

DNA-bindenden abh&#xE4;ngige und unabh&#xE4;ngige Funktionen von WT1-Protein w&#xE4;hrend der menschlichen H&#xE4;matopoese.

The discovery of a major hematopoietic stem cell (HSC) pool in mid-gestation mouse placenta has defined the placenta as yet another important anatomical site that participates in HSC development. Placental HSC activity starts in parallel with the AGM region, before HSCs are found in circulation or have colonized the fetal liver. Moreover, placental hematopoietic activity culminates in a rapid expansion of the definitive HSC pool, which occurs during the time when the fetal liver HSC reservoir begins to grow. Furthermore, hematopoietic cells in mid-gestation mouse placenta are not instructed for differentiation along the myeloerythroid lineage, as in the fetal liver. These findings suggest that the placenta provides a supportive niche where the definitive hematopoietic stem cell pool can be temporarily established during development. Future studies are needed to characterize the developmental events that lead to the establishment of placental HSC pool, and to define the microenvironmental signals that support this process. Furthermore, if the stem cell-promoting properties of the placental niche can be harnessed in vitro to support HSC formation, maturation, and/or expansion in culture, these assets may greatly improve hematopoietic stem cell-based therapies in the future.

Placenta as a site for hematopoietic stem cell development.

Plazenta als Standort f&#xFC;r h&#xE4;matopoetische Stammzelle Entwicklung.

The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow (BM) stem/progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (Flt3) ligand (Fl)-deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor alpha (IL-7Ralpha) signaling. Fl-/-Il-7r-/- mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7Ralpha-independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7Ralpha, in regulation of the earliest lineage-negative (Lin(-)) Lin(-)SCA1+KIT+ (LSK) FLT3(hi) lymphoid-primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors.

Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors.

Die molekularen Bahnen, die Regulierung der lymphatischen Grundierung, Schicksal und die Entwicklung von multipotenten Knochenmark (BM) Vorbau/Progenitorzellen, die kontinuierlich Thymom Vorl&auml;uferzellen zu ersetzen, bleiben weitgehend unbekannt. Hier zeigen wir, dass Fms-wie Tyrosinkinase 3 (Flt3) Ligand (Fl)-unzul&auml;ngliche M&auml;usen haben deutliche K&uuml;rzungen in den fr&uuml;hesten Thymom Vorl&auml;uferzellen im fetalen und postnatale Erwachsenen Thymus. Eine kritische Rolle von FL in Thymopoiesis zeigte sich insbesondere in Ermangelung Interleukin-7-Rezeptor Alpha (IL-7Ralpha) zu signalisieren. FL-/-Il-7r-/-M&auml;use haben umfangreiche K&uuml;rzungen im fetalen und postnatale Thymom Vorl&auml;uferzellen, die einem Verlust des aktiven Thymopoiesis bei Erwachsenen M&auml;usen demonstriert eine unverzichtbare Rolle der FL in IL-7Ralpha-unabh&auml;ngige fetalen und adulten T Lymphopoiesis. Dar&uuml;ber hinaus schaffen wir eine einzigartige und kritische Rolle der FL, von IL-7Ralpha, in der Verordnung des fr&uuml;hesten Herkunfts-negativen (Lin(-)) Lin (-) SCA1 + KIT + (LSK) FLT3(hi) lymphatischen grundiert multipotenten Vorl&auml;uferzellen in BM, demonstriert eine Schl&uuml;sselrolle des FLT3 Signalisierung bei der Regulierung von der sehr fr&uuml;hesten Stadien der lymphatischen Vorl&auml;uferzellen.

Entscheidende Rolle von FLT3 Ligand in IL-7-Rezeptor-unabh&auml;ngige T Lymphopoiesis und Regulierung des lymphatischen grundiert multipotenten Vorl&auml;uferzellen.

The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a heartbeat, verified that HSC development is initiated in the placental vasculature independent of blood flow. However, fewer CD41+ hematopoietic cells were found in Ncx1(-/-) placentas than in controls, implying that some HSCs/progenitors colonize the placenta via circulation and/or HSC emergence is compromised without blood flow. Importantly, placentas from Ncx1(-/-) embryos possessed equal potential to generate myelo-erythroid and B and T lymphoid cells upon explant culture, verifying intact multilineage hematopoietic potential, characteristic of developing HSCs. These data suggest that, in addition to providing a niche for a large pool of HSCs prior to liver colonization, the placenta is a true site of HSC generation.

The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation.

Die Maus-Plazenta enth&uuml;llt sich als ein wichtiges Reservoir f&uuml;r h&auml;matopoetische Stammzellen (HSCs), aber der Ursprung der Plazenta HSCs unbekannt war. Durch die Verfolgung durch Ausdruck der Runx1-LacZ und CD41 HSCs zu entwickeln, haben wir festgestellt, dass HSCs in gro&szlig;e Gef&auml;&szlig;e in der Plazenta entstehen. Analyse der Ncx1(-/-) Embryonen, die es an einen Herzschlag fehlt, &uuml;berpr&uuml;ft, ob die HSC-Entwicklung in der Plazenta Gef&auml;&szlig;system unabh&auml;ngig von Blutfluss initiiert wird. Jedoch weniger CD41 + h&auml;matopoetische Zellen im Ncx1(-/-) Plazenta gefunden als in Steuerelementen, was bedeutet, dass einige HSCs/Vorfahre die Plazenta &uuml;ber Verkehr und/oder HSC-Entstehung kolonisieren ohne Blutfluss beeintr&auml;chtigt wird. Wichtiger ist, besa&szlig; die Plazenta aus Ncx1(-/-) Embryonen gleich Potenzial Myelo-Erythroid und B und T lymphoide Zellen auf Explant Kultur, &Uuml;berpr&uuml;fen der intakten multiline&auml;rer h&auml;matopoetischen Potenzial, charakteristisch f&uuml;r die Entwicklung von HSCs generieren. Diese Daten legen nahe, dass, neben eine Nische f&uuml;r einen gro&szlig;en Pool von HSCs vor der Leber Kolonisation, die Plazenta eine echte Website HSC-Generation.

Die Entstehung von h&auml;matopoetischen Stammzellen wird in der Plazenta Gef&auml;&szlig;system in Ermangelung der Zirkulation initiiert.

Forced expression of the four transcription factors Oct4, Sox2, c-Myc, and Klf4 is sufficient to confer a pluripotent state upon the murine fibroblast genome, generating induced pluripotent stem (iPS) cells. Although the differentiation potential of these cells is thought to be equivalent to that of embryonic stem (ES) cells, it has not been rigorously determined. In this study, we sought to identify the capacity of iPS cells to differentiate into Flk1-positive progenitors and their mesodermal progeny, including cells of the cardiovascular and hematopoietic lineages. Immunostaining of tissues from iPS cell-derived chimeric mice demonstrated that iPS cells could contribute in vivo to cardiomyocytes, smooth muscle cells, endothelial cells, and hematopoietic cells. To compare the in vitro differentiation potential of murine ES and iPS cells, we either induced embryoid body (EB) formation of each cell type or cultured the cells on collagen type IV (ColIV), an extracellular matrix protein that had been reported to direct murine ES cell differentiation to mesodermal lineages. EB formation and exposure to ColIV both induced iPS cell differentiation into cells that expressed cardiovascular and hematopoietic markers. To determine whether ColIV-differentiated iPS cells contained a progenitor cell with cardiovascular and hematopoietic differentiation potential, Flk1-positive cells were isolated by magnetic cell sorting and exposed to specific differentiation conditions, which induced differentiation into functional cardiomyocytes, smooth muscle cells, endothelial cells, and hematopoietic cells. Our data demonstrate that murine iPS cells, like ES cells, can differentiate into cells of the cardiovascular and hematopoietic lineages and therefore may represent a valuable cell source for applications in regenerative medicine. Disclosure of potential conflicts of interest is found at the end of this article.

Reprogrammed mouse fibroblasts differentiate into cells of the cardiovascular and hematopoietic lineages.

Gezwungen Ausdruck der vier Transkriptionsfaktoren Oct4, Sox2, reicht c-Myc und Klf4 um einen pluripotenten Zustand auf das murine Fibroblasten-Genom, verleihen Generieren von induzierten pluripotenten Stammzellen (iPS). Obwohl das Differenzierung Potenzial dieser Zellen angenommen wird, entspricht der embryonalen Stammzellen (ES), wurde es nicht streng festgelegt. Wir wollten in dieser Studie identifizieren, die Kapazit&auml;t der iPS-Zellen, in Flk1-positiven Vorl&auml;uferzellen und mesodermale nachkommen, einschlie&szlig;lich der sogenannten kardiovaskul&auml;ren und h&auml;matopoetischen Zellen zu unterscheiden. Immunf&auml;rbung von Gewebe von IPS-Zellen abgeleitete chimeric M&auml;use zeigten, dass iPS-Zellen in-vivo Cardiomyocytes, glatten Muskelzellen und Endothelzellen blutbildender Zellen beitragen k&ouml;nnte. F&uuml;r einen Vergleich das in-vitro-Differenzierung Potenzial der murinen es- und iPS-Zellen induziert wir entweder Embryoid K&ouml;rper (EB) Bildung von jeder Zellart oder kultivierten Zellen Kollagen Typ IV (ColIV), eine extrazellul&auml;re Matrix-Protein, das murine ES direkte berichtet worden war-Zell-Differenzierung mesodermale &Uuml;bertragungslinien. EB-Entstehung und Gef&auml;hrdung durch ColIV induzierte beide iPS Zelldifferenzierung in Zellen, die Herz-Kreislauf- und h&auml;matopoetischen Marker ausgedr&uuml;ckt. Um festzustellen, ob ColIV getrennte iPS-Zellen eine Zelle Vorl&auml;uferzellen mit Herz-Kreislauf- und h&auml;matopoetischen Differenzierung potenzielle enthalten, waren Flk1-positiven Zellen isoliert von magnetischen Zellsortierung und Differenzierung der spezifischen Bedingungen, die Unterscheidung in funktionale Cardiomyocytes, glatten Muskelzellen und Endothelzellen blutbildender Zellen induziert ausgesetzt. Unsere Daten zeigen, dass murinen iPS-Zellen, wie ES-Zellen, in Zellen der Herz-Kreislauf- und h&auml;matopoetischen Linien unterscheiden k&ouml;nnen und daher m&ouml;glicherweise eine wertvolle Zelle Quelle f&uuml;r Anwendungen in der regenerativen Medizin dar. Offenlegung von m&ouml;glichen Interessenkonflikten findet sich am Ende dieses Artikels.

Umprogrammiert Maus-Fibroblasten differenzieren sich in der sogenannten kardiovaskul&auml;ren und blutbildender Zellen.

Etablierte vaskul&auml;re Risikofaktoren (ie, Rauchen, Bluthochdruck, Diabetes Mellitus und Dyslipid&auml;mie) spielen eine wichtige Rolle bei der Entwicklung von Gef&auml;&szlig;erkrankungen. Anzeichen daf&uuml;r deutet darauf hin, dass m&ouml;glicherweise einige dieser Risikofaktoren eine intensivere Wirkung auf bestimmten arteriellen Betten, Feststellung, die Auswirkungen auf eine prognostische Rolle f&uuml;r bestimmte Typen von Gef&auml;&szlig;erkrankungen enth&auml;lt.

Wirken verschiedene vaskul&auml;re Risikofaktoren ebenso alle Arterien?

Established vascular risk factors (ie, smoking, hypertension, diabetes mellitus, and dyslipidemia) play an important role in the development of vascular disease. Emerging evidence suggests that some of these risk factors may have a more intense effect on specific arterial beds, a finding that holds implications for a prognostic role for certain types of vascular disease.

Do different vascular risk factors affect all arteries equally?

Cardiovascular risk factor modification: a sine qua non in the management of vascular surgery patients.

Kardiovaskul&auml;ren Risikofaktor &Auml;nderung: conditio Sine Qua Non bei der Verwaltung der Gef&auml;&szlig;chirurgie Patienten.

Erectile dysfunction in stroke patients: a multifactorial problem with important psychosocial consequences.

Erektile Dysfunktion bei Schlaganfallpatienten: multifaktorielle Probleme mit erheblichen psychosozialen Konsequenzen.

This unit describes the isolation of hematopoietic stem cells (HSCs) from the mouse placenta. The placenta was recently identified as an important hematopoietic site that generates HSCs de novo and provides a transitory niche for a large pool of HSCs during midgestation. This protocol includes a dissection technique for murine placenta, the mechanical and enzymatic steps of placental tissue dissociation, and phenotypical identification and isolation of HSCs. It also contains a method for immunohistochemical analysis of placenta tissue sections to visualize developing HSCs in the placenta.

Isolation and visualization of mouse placental hematopoietic stem cells.

Diese Ma&szlig;einheit beschreibt die Isolation von h&auml;matopoetischen Stammzellen (HSCs) von der Maus-Plazenta. Die Plazenta wurde vor kurzem als ein wichtiger Standort der h&auml;matopoetischen identifiziert, generiert HSCs de Novo und sieht eine vor&uuml;bergehende Nische einen gro&szlig;en Pool von HSCs bei Midgestation. Dieses Protokoll enth&auml;lt eine Dissektion-Technik f&uuml;r murine Plazenta, die mechanische und enzymatische Schritte von Plazenta-Gewebe Dissoziation, und ph&auml;notypische Identifizierung und Isolierung von HSCs. Er enth&auml;lt auch eine Methode f&uuml;r Immunohistochemical Analyse von Plazenta-Gewebe-Abschnitte zu visualisieren, Entwicklung von HSCs in der Plazenta.

Isolierung und Visualisierung der Maus Plazenta hematopoietic Stammzellen.

A 75-year old man presented with signs and symptoms of acute abdomen and a clinical picture of hypovolemic shock. An emergency CT scan revealed a ruptured para-anastomotic left common iliac artery aneurysm. The patient had undergone an elective abdominal aortic aneurysm repair operation and placement of an aortoiliac bifurcated graft 10 years before. Para-anastomotic aneurysms had developed in all 3 (aortic and the 2 iliac) anastomosis. As the patient was highrisk, a combined endovascular/surgical approach was undertaken. The patient was discharged 4 days later.This article discusses the applicability of endovascular procedures in emergency settings to high-risk patients.

Combined endovascular/surgical management of a ruptured para-anastomotic aneurysm of the left common iliac artery.

Ein 75 - Jahre alter Mann mit Zeichen und Symptome der akuten Bauch und ein Krankheitsbild der Hypovol&auml;mie Schock dargestellt. Ein Notfall CT-Scan zeigte einen geplatzten Para-anastomotic linken gemeinsame iliaca Aneurysma. Der Patient hatte eine elektiven Aortenaneurysma, abdominales-Reparatur-Operation unterzogen und Platzierung der eine arterielle Transportkomponente Pfropfen 10 Jahre vor. Para-anastomotic Aneurysmen in alle 3 entwickelt hatte (Aorta und die Arteria iliaca 2) Anastomose. Wie der Patient einem war, war ein kombinierter endovaskul&auml;re/chirurgische Ansatz verpflichtet. Der Patient wurde 4 Tage sp&auml;ter entlassen.Dieser Artikel beschreibt die Anwendbarkeit der endovaskul&auml;re im Notfall Einstellungen f&uuml;r Patienten mit hohem Risiko.

Kombinierte endovaskul&auml;re/chirurgische Management eine geplatzte Para-anastomotic Aneurysma der linken iliaca communis.

The placenta is a highly vascularized organ that mediates fetal-maternal exchange during pregnancy and is thereby vital for the survival and growth of the developing embryo. In addition to having this well-established role in supporting pregnancy, the placenta was recently shown to function as a hematopoietic organ. The placenta is unique among other fetal hematopoietic organs, as it is capable of both generating multipotential hematopoietic cells de novo and establishing a major hematopoietic stem cell (HSC) pool in the conceptus, while protecting HSCs from premature differentiation. The mouse placenta contains two distinct vascular regions that support hematopoiesis: the large vessels in the chorionic plate where HSCs/progenitors are thought to emerge and the labyrinth vasculature where nascent HSCs/progenitors may colonize for expansion and possible functional maturation. Defining how this cytokine- and growth factor rich organ supports HSC generation, maturation and expansion may ultimately help to establish culture protocols for HSC expansion or de novo generation from pluripotent cells.

Hematopoietic stem cell development in the placenta.

Die Plazenta ist ein h&ouml;chst gef&auml;&szlig;reichen Organ, die vermittelt fetalen und m&uuml;tterlichen Austausch w&auml;hrend der Schwangerschaft und ist damit entscheidend f&uuml;r das &Uuml;berleben und Wachstum des Embryos entwickeln. Zus&auml;tzlich zu diesem etablierten Rolle bei der Unterst&uuml;tzung der Schwangerschaft, wurde die Plazenta vor kurzem als Organ der h&auml;matopoetischen Funktion gezeigt. Die Plazenta ist einzigartig unter den anderen fetalen h&auml;matopoetischen Organe, wie es generieren multipotenzielle blutbildender Zellen de Novo und Einrichtung eines gro&szlig;en h&auml;matopoetische Stammzellen (HSC)-Pools in die Conceptus gleichzeitig HSCs vor vorzeitiger Differenzierung zu sch&uuml;tzen. Die Maus-Plazenta enth&auml;lt zwei verschiedene vaskul&auml;re Regionen, die Blutbildung unterst&uuml;tzen: die gro&szlig;en Schiffe in die Chorionkarzinome Platte wo HSCs/Vorfahre gedacht werden, um das entstehen und die Labyrinth-Gef&auml;&szlig;system wo entstehende HSCs/Vorl&auml;uferzellen f&uuml;r Ausbau und m&ouml;gliche funktionelle Reifung kolonisieren k&ouml;nnen. Definieren Sie, wie diese Cytokine und Wachstumsfaktor reichen Orgel HSC-Generation unterst&uuml;tzt, k&ouml;nnen Reifung und Expansion letztlich helfen, Protokolle f&uuml;r HSC-Expansion oder de Novo Erzeugung von pluripotenten Zellen herzustellen.

H&auml;matopoetische Stammzelle-Entwicklung in der Plazenta.

The era of induced pluripotent stem (iPS) cells carries with it the promise of virtually unlimited sources of autologous cells for regenerative medicine. However, efficiently differentiating iPS cells into fully functional mature cell types remains challenging. A new study reporting the formation of fully functional platelets from human iPS (hiPS) cells improves upon recent efforts to generate this enucleated cell type, which remains in high demand for therapeutic transfusions. Notably, their lack of nucleus renders platelets unable to retain the pluripotent or tumorigenic properties of iPS cells.

Induced pluripotent stem cell-derived human platelets: one step closer to the clinic.

Die &Auml;ra der induzierten pluripotenten Stammzellen (iPS) birgt das Versprechen der nahezu unbegrenzten Quellen f&uuml;r autologe Zellen f&uuml;r die regenerative Medizin. Jedoch effizient Differenzierung iPS-Zellen in voll funktionsf&auml;hige Reife Zelle Arten bleibt herausfordernd. Eine neue Studie, die Berichterstattung, dass die Bildung von voll funktionsf&auml;hige Thrombozyten aus menschlichen iPS (HiPS) Zellen auf die j&uuml;ngsten Bem&uuml;hungen, die dadurch generiert verbessert enucleated Zelltyp, die in der hohen Nachfrage f&uuml;r therapeutische Transfusionen bleibt. Bemerkenswert ist, rendert ihre mangelnde Kern Thrombozyten die pluripotenten oder tumorigenic Eigenschaften des iPS-Zellen nicht beibehalten.

Article	Year
Anatomical variation of co-existence of 4th and 5th short metacarpal bones, sesamoid ossicles and exostoses of ulna and radius in the same hand: a case report. Cases journal\| PubMed ID: 18959780	2008
Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis. Blood\| PubMed ID: 19211936	2009
Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development. Blood\| PubMed ID: 15677556	2005
The placenta is a niche for hematopoietic stem cells. Developmental cell\| PubMed ID: 15737932	2005
DNA-binding dependent and independent functions of WT1 protein during human hematopoiesis. Experimental cell research\| PubMed ID: 15907324	2005
Placenta as a site for hematopoietic stem cell development. Experimental hematology\| PubMed ID: 16140153	2005
Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors. Blood\| PubMed ID: 17540845	2007
The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell stem cell\| PubMed ID: 18371450	2008
Reprogrammed mouse fibroblasts differentiate into cells of the cardiovascular and hematopoietic lineages. Stem cells (Dayton, Ohio)\| PubMed ID: 18450826	2008
Do different vascular risk factors affect all arteries equally? Angiology\| PubMed ID: 18505745	2008
Cardiovascular risk factor modification: a sine qua non in the management of vascular surgery patients. Current vascular pharmacology\| PubMed ID: 18673155	2008
Erectile dysfunction in stroke patients: a multifactorial problem with important psychosocial consequences. International urology and nephrology\| PubMed ID: 18683073	2008
Isolation and visualization of mouse placental hematopoietic stem cells. Current protocols in stem cell biology\| PubMed ID: 18729047	2008
Combined endovascular/surgical management of a ruptured para-anastomotic aneurysm of the left common iliac artery. The open cardiovascular medicine journal\| PubMed ID: 19834625	2009
Hematopoietic stem cell development in the placenta. The International journal of developmental biology\| PubMed ID: 20711986	2010
Induced pluripotent stem cell-derived human platelets: one step closer to the clinic. The Journal of experimental medicine\| PubMed ID: 21173109	2010

Christos Gekas

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