Robert Sackstein

Brigham and Women's Hospital, Boston, Massachusetts, United States

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Publications (105)644.38 Total impact

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    ABSTRACT: Neural stem cell (NSC)-based therapies offer potential for neural repair in CNS inflammatory and degenerative disorders. Typically, these conditions present with multifocal CNS lesions making it impractical to inject NSCs locally, thus mandating optimization of vascular delivery of the cells to involved sites. Here we analyzed NSCs for expression of molecular effectors of cell migration and found that these cells are natively devoid of E-selectin ligands. Using glycosyltransferase-programmed stereosubstitution (GPS), we glycan engineered the cell surface of NSCs ("GPS-NSC") with resultant enforced expression of the potent E-selectin ligand HCELL and of an E-selectin-binding glycoform of NCAM ("NCAM-E"). Following intravenous injection, short-term homing studies demonstrated that, compared to buffer treated (control)-NSCs (BT-NSCs), GPS-NSCs showed greater neurotropism. Administration of GPS-NSC significantly attenuated the clinical course of Experimental Autoimmune Encephalomyelitis (EAE), with markedly decreased inflammation and improved oligodendroglial and axonal integrity, but without evidence of long-term stem cell engraftment. Notably, this effect of NSC is not a universal property of adult stem cells, as administration of GPS-engineered mouse hematopoietic stem/progenitor cells did not improve EAE clinical course. These findings highlight the utility of cell surface glycan engineering to boost stem cell delivery in neuroinflammatory conditions, and indicate that despite the use of a neural tissue-specific progenitor cell population, neural repair in EAE results from endogenous repair and not from direct, NSC-derived cell replacement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Glycobiology 07/2015; DOI:10.1093/glycob/cwv046 · 3.14 Impact Factor
  • Jungmin Lee · Brad Dykstra · Robert Sackstein · Derrick J Rossi
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    ABSTRACT: Human pluripotent stem cells (PSCs) have the potential to provide an inexhaustible source of hematopoietic stem cells (HSCs) that could be used in disease modeling and in clinical applications such as transplantation. Although the goal of deriving definitive HSCs from PSCs has not been achieved, recent studies indicate that progress is being made. This review will provide information on the current status of deriving HSCs from PSCs, and will highlight existing challenges and obstacles. Recent strides in HSC generation from PSCs has included derivation of developmental intermediates, identification of transcription factors and small molecules that support hematopoietic derivation, and the development of strategies to recapitulate niche-like conditions. Despite considerable progress in defining the molecular events driving derivation of hematopoietic progenitor cells from PSCs, the generation of robust transplantable HSCs from PSCs remains elusive. We propose that this goal can be facilitated by better understanding of the regulatory pathways governing HSC identity, development of HSC supportive conditions, and examining the marrow homing properties of PSC-derived HSCs.
    Current opinion in hematology 07/2015; 22(4):317-323. DOI:10.1097/MOH.0000000000000147 · 4.05 Impact Factor
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    ABSTRACT: Type 1 diabetes (T1D) is an immune-mediated disease resulting in destruction of insulin-producing pancreatic beta cells. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties, garnering increasing attention as cellular therapy for T1D and other immunologic diseases. However, MSCs generally lack homing molecules, hindering their colonization at inflammatory sites following intravenous (IV) administration. Here we analyzed whether enforced E-selectin ligand expression on murine MSCs could impact their effect in reversing hyperglycemia in non-obese diabetic (NOD) mice. Though murine MSCs natively do not express the E-selectin binding determinant sialyl Lewisx (sLex), we found that fucosyltransferase-mediated α(1,3)-exofucosylation of murine MSCs resulted in sLex display uniquely on cell surface CD44 thereby creating HCELL, the E-selectin-binding glycoform of CD44. Following IV infusion into diabetic NOD mice, allogeneic HCELL+ MSCs showed 3-fold greater peri-islet infiltrates compared to buffer-treated (i.e., HCELL- ) MSCs, with distribution in proximity to E-selectin-expressing microvessels. Exofucosylation had no effect on MSC immunosuppressive capacity in in vitro assays, however, though engraftment was temporary for both HCELL+ and HCELL- MSCs, administration of HCELL+ MSCs resulted in durable reversal of hyperglycemia, whereas only transient reversal was observed following administration of HCELL- MSCs. Notably, exofucosylation of MSCs generated from CD44-/- mice induced prominent membrane expression of sLex, but IV administration of these MSCs into hyperglycemic NOD mice showed no enhanced pancreatotropism or reversal of hyperglycemia. These findings provide evidence that glycan engineering to enforce HCELL expression boosts trafficking of infused MSCs to pancreatic islets of NOD mice and substantially improves their efficacy in reversing autoimmune diabetes. This article is protected by copyright. All rights reserved.
    Stem Cells 01/2015; 33(5). DOI:10.1002/stem.1948 · 7.70 Impact Factor
  • Cristina I Silvescu · Robert Sackstein
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    ABSTRACT: The host defense response critically depends on the production of leukocytes by the marrow and the controlled delivery of these cells to relevant sites of inflammation/infection. The cytokine granulocyte-colony stimulating factor (G-CSF) is commonly used therapeutically to augment neutrophil recovery following chemo/radiation therapy for malignancy, thereby decreasing infection risk. Although best known as a potent inducer of myelopoiesis, we previously reported that G-CSF also promotes the delivery of leukocytes to sites of inflammation by stimulating expression of potent E-selectin ligands, including an uncharacterized ∼65-kDa glycoprotein. To identify this ligand, we performed integrated biochemical analysis and mass spectrometry studies of G-CSF-treated primary human myeloid cells. Our studies show that this novel E-selectin ligand is a glycoform of the heavy chain component of the enzyme myeloperoxidase (MPO), a well-known lysosomal peroxidase. This specialized MPO glycovariant, referred to as "MPO-E-selectin ligand" (MPO-EL), is expressed on circulating G-CSF-mobilized leukocytes and is naturally expressed on blood myeloid cells in patients with febrile leukocytosis. In vitro biochemical studies show that G-CSF programs MPO-EL expression on human blood leukocytes and marrow myeloid cells via induction of N-linked sialofucosylations on MPO, with concomitant cell surface display of the molecule. MPO-EL is catalytically active and mediates angiotoxicity on human endothelial cells that express E-selectin. These findings thus define a G-CSF effect on MPO chemical biology that endows unsuspected functional versatility upon this enzyme, unveiling new perspectives on the biology of G-CSF and MPO, and on the role of E-selectin receptor/ligand interactions in leukocyte migration and vascular pathology.
    Proceedings of the National Academy of Sciences 07/2014; 111(29). DOI:10.1073/pnas.1320833111 · 9.81 Impact Factor
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    ABSTRACT: Whereas DC have increasingly been recognized for their role in activating the inflammatory cascades during IRIs, the mechanisms by which oxidative stress enhances DC activation remain to be explored. We examined the role of oxidative stress on two important features of DC: T cell activation and trafficking. Bone marrow-derived OS-DC were compared with untreated DC. DC exposed to oxidative stress augmented allogeneic T cell proliferation and showed increased migration in a chemotaxis chamber. These results were confirmed by using hypoxanthine and xanthine oxidase as another inducer of oxidative stress. We used OT-II and OT-I mice to assess the effect of oxidative stress on DC activation of OVA-specific CD4(+) and CD8(+) T cells, respectively. Oxidative stress increased DC capacity to promote OVA-specific CD4(+) T cell activity, demonstrated by an increase in their proliferation and production of IFN-γ, IL-6, and IL-2 proinflammatory cytokines. Whereas oxidative stress increased the DC ability to stimulate IFN-γ production by OVA-specific CD8(+) T cells, cellular proliferation and cytotoxicity were not affected. Compared with untreated DC, oxidative stress significantly reduced the capacity of DC to generate Tregs, which were restored by using anti-IL-6. With regard to DC trafficking, whereas oxidative stress increased DC expression of p-Akt and p-NF-κB, targeting PI3Kγ and NF-κB pathways abrogated the observed increase in DC migration. Our data propose novel insights on the activation of DC by oxidative stress and provide rationales for targeted therapies, which can potentially attenuate IRI.
    Journal of leukocyte biology 03/2014; 96(2). DOI:10.1189/jlb.3A0113-033RR · 4.99 Impact Factor
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    ABSTRACT: Leukocyte adhesion deficiency type-II (LADII) is a hereditary disorder of neutrophil migration caused by mutations in the GDP-fucose transporter gene (SLC35C1). In these patients, inability to generate key fucosylated molecules including sialyl Lewis X leads to leukocytosis and recurrent infections, in addition to short stature and developmental delay. We report two brothers with short stature and developmental delay who are compound heterozygotes for novel mutations in SLC35C1 resulting in partial in vivo defects in fucosylation. Specifically, plasma glycoproteins including IgG demonstrated marked changes in glycoform distribution. While neutrophil rolling on endothelial selectins was partially impeded, residual adhesion proved sufficient to avoid leukocytosis or recurrent infection. These findings demonstrate a surprising degree of immune redundancy in the face of substantial alterations in adhesion molecule expression, while showing that short stature and developmental delay may be the sole presenting signs in this disorder.
    Human Molecular Genetics 01/2014; 23(11). DOI:10.1093/hmg/ddu001 · 6.68 Impact Factor
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    ABSTRACT: Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between stem/progenitor cells that proliferate or differentiate and somatic cells of the lung, we used a novel organotypic ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free-floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3 and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conservative population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. More than 50% of the AIC population was c-KIT(+) or double-positive for CD45(+) and CD11b(+) antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. At the air/gel interface, AICs undergo remodeling to form a cellular lining, whereas TGF(β)1 treatment modifies protein expression properties to further imply a robust effect of the microenvironment on AIC phenotypic changes. These data confirm the active participation of clonogenic hematopoietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which license sustained cell viability, proliferation and differentiation, for use in studies of compensatory pulmonary growth. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 07/2013; 7(7). DOI:10.1002/term.553 · 4.43 Impact Factor
  • Robert Sackstein
    Experimental hematology 04/2012; 40(7):518-9; author reply 519-20. DOI:10.1016/j.exphem.2012.03.004 · 2.81 Impact Factor
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    Robert Sackstein
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    ABSTRACT: The proximate hurdle for cell trafficking to any anatomic site is the initial attachment of circulating cells to target tissue endothelium with sufficient strength to overcome prevailing forces of blood flow. E-selectin, an endothelial molecule that is inducibly expressed at all sites of inflammation, is a potent effector of this primary braking process. This molecule is a member of a family of C-type lectins known as selectins that bind sialofucosylated glycans displayed on either a protein (i.e., glycoprotein) or lipid (i.e., glycolipid) scaffold. On human cells, the predominant E-selectin ligand is a specialized glycoform of CD44 known as hematopoietic cell E-/L-selectin ligand (HCELL). This review focuses on the biology of HCELL/E-selectin interactions in cell migration, and discusses the utility and applicability of glycosyltransferase-programmed stereosubstitution (GPS) for glycoengineering HCELL expression. Without compromising cell viability or native phenotype, this exoglycosylation technology literally "sweetens" CD44, licensing E-selectin-dependent vascular delivery for all cell-based therapeutics.
    Annals of the New York Academy of Sciences 02/2012; 1253(1):193-200. DOI:10.1111/j.1749-6632.2011.06421.x · 4.31 Impact Factor
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    ABSTRACT: When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17(ΔZn/ΔZn) platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage.
    Blood 11/2011; 119(5):1263-73. DOI:10.1182/blood-2011-05-355628 · 10.43 Impact Factor
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    Robert Sackstein
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    ABSTRACT: The successful clinical implementation of adoptive cell therapeutics, including bone marrow transplantation and other stem cell-based treatments, depends critically on the ability to deliver cells to sites where they are needed. E-selectin, an endothelial C-type lectin, binds sialofucosylated carbohydrate determinants on its pertinent ligands. This molecule is expressed in a constitutive manner on bone marrow and dermal microvascular endothelium, and inducibly on post-capillary venules at all sites of tissue injury. Engagement of E-selectin with relevant ligand(s) expressed on circulating cells mediates initial "tethering/rolling" endothelial adhesive interactions prerequisite for extravasation of blood-borne cells at any target tissue. Most mammalian cells express high levels of a transmembrane glycoprotein known as CD44. A specialized glycoform of CD44 called "Hematopoietic Cell E-/L-selectin Ligand" (HCELL) is a potent E-selectin ligand expressed on human cells. Under native conditions, HCELL expression is restricted to human hematopoietic stem/progenitor cells. We have developed a technology called "Glycosyltransferase-Programmed Stereosubstitution" (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells. GPS-based glycoengineering of HCELL endows cell migration to endothelial beds expressing E-selectin. Enforced HCELL expression targets human mesenchymal stem cell homing to marrow, licensing transendothelial migration without chemokine signaling via a VLA-4/VCAM-1-dependent "Step 2-bypass pathway." This review presents an historical framework of the homing receptor concept, and will describe the discovery of HCELL, its function as the bone marrow homing receptor, and how enforced expression of this molecule via chemical engineering of CD44 glycans could enable stem cell-based regenerative medicine and other adoptive cell therapeutics.
    Annals of Biomedical Engineering 11/2011; 40(4):766-76. DOI:10.1007/s10439-011-0461-8 · 3.23 Impact Factor
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    Pieter P Jacobs · Robert Sackstein
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    ABSTRACT: Despite great strides in our knowledge of the genetic and epigenetic changes underlying malignancy, we have limited information on the molecular basis of metastasis. Over 90% of cancer deaths are caused by spread of tumor cells from a primary site to distant organs and tissues, highlighting the pressing need to define the molecular effectors of cancer metastasis. Mounting evidence suggests that circulating tumor cells (CTCs) home to specific tissues by hijacking the normal leukocyte trafficking mechanisms. Cancer cells characteristically express CD44, and there is increasing evidence that hematopoietic cell E-/L-selectin ligand (HCELL), a sialofucosylated glycoform of CD44, serves as the major selectin ligand on cancer cells, allowing interaction of tumor cells with endothelium, leukocytes, and platelets. Here, we review the structural biology of CD44 and of HCELL, and present current data on the function of these molecules in mediating organ-specific homing/metastasis of CTCs.
    FEBS letters 08/2011; 585(20):3148-58. DOI:10.1016/j.febslet.2011.07.039 · 3.34 Impact Factor
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    Robert Sackstein
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    ABSTRACT: The homing and egress of hematopoietic stem and progenitor cells (HSPCs) to and from marrow, respectively, and the proliferation and differentiation of HSPCs within marrow are complex processes critically regulated by the ordered expression and function of adhesion molecules that direct key cell-cell and cell-matrix interactions. The integral membrane molecule CD44, known primarily for its role in binding hyaluronic acid, is characteristically expressed on HSPCs. Conspicuously, human HSPCs uniquely display a specialized glycoform of CD44 known as hematopoietic cell E-/L-selectin ligand (HCELL), which is the most potent ligand for both E-selectin and L-selectin expressed on human cells. This review focuses on recent advances in our understanding of the biology of CD44 and HCELL in hematopoiesis. New data indicate that CD44-mediated events in hematopoiesis are more complex than previously imagined. Ex-vivo glycan engineering has established that HCELL serves as a 'bone marrow homing receptor'. Moreover, biochemical studies now show that CD44 forms bimolecular complexes with a variety of membrane proteins, one of which is VLA-4. Engagement of CD44 or of HCELL directly induces VLA-4 activation via G-protein-dependent signaling, triggering a 'step 2-bypass pathway' of cell migration, and extravascular lodgment, in absence of chemokine receptor engagement. Recent studies have further clarified the roles of CD44 and its glycoform HCELL in hematopoietic processes, providing key insights on how targeting these molecules may be beneficial in promoting hematopoiesis and in treating hematologic malignancies.
    Current opinion in hematology 07/2011; 18(4):239-48. DOI:10.1097/MOH.0b013e3283476140 · 4.05 Impact Factor
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    ABSTRACT: Although well recognized that expression of E-selectin on marrow microvessels mediates osteotropism of hematopoietic stem/progenitor cells (HSPCs), our knowledge regarding the cognate E-selectin ligand(s) on HSPCs is incomplete. Flow cytometry using E-selectin-Ig chimera (E-Ig) shows that human marrow cells enriched for HSPCs (CD34(+) cells) display greater E-selectin binding than those obtained from mouse (lin(-)/Sca-1(+)/c-kit(+) [LSK] cells). To define the relevant glycoprotein E-selectin ligands, lysates from human CD34(+) and KG1a cells and from mouse LSK cells were immunoprecipitated using E-Ig and resolved by Western blot using E-Ig. In both human and mouse cells, E-selectin ligand reactivity was observed at ~ 120- to 130-kDa region, which contained two E-selectin ligands, the P-selectin glycoprotein ligand-1 glycoform "CLA," and CD43. Human, but not mouse, cells displayed a prominent ~ 100-kDa band, exclusively comprising the CD44 glycoform "HCELL." E-Ig reactivity was most prominent on CLA in mouse cells and on HCELL in human cells. To further assess HCELL's contribution to E-selectin adherence, complementary studies were performed to silence (via CD44 siRNA) or enforce its expression (via exoglycosylation). Under physiologic shear conditions, CD44/HCELL-silenced human cells showed striking decreases (> 50%) in E-selectin binding. Conversely, enforced HCELL expression of LSK cells profoundly increased E-selectin adherence, yielding > 3-fold more marrow homing in vivo. These data define the key glycoprotein E-selectin ligands of human and mouse HSPCs, unveiling critical species-intrinsic differences in both the identity and activity of these structures.
    Blood 06/2011; 118(7):1774-83. DOI:10.1182/blood-2010-11-320705 · 10.43 Impact Factor
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    Sai P Thankamony · Robert Sackstein
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    ABSTRACT: According to the multistep model of cell migration, chemokine receptor engagement (step 2) triggers conversion of rolling interactions (step 1) into firm adhesion (step 3), yielding transendothelial migration. We recently reported that glycosyltransferase-programmed stereosubstitution (GPS) of CD44 on human mesenchymal stem cells (hMSCs) creates the E-selectin ligand HCELL (hematopoietic cell E-selectin/L-selectin ligand) and, despite absence of CXCR4, systemically administered HCELL(+)hMSCs display robust osteotropism visualized by intravital microscopy. Here we performed studies to define the molecular effectors of this process. We observed that engagement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesion to ligand VCAM-1. This VLA-4 activation is mediated via a Rac1/Rap1 GTPase signaling pathway, resulting in transendothelial migration on stimulated human umbilical vein endothelial cells without chemokine input. These findings indicate that hMSCs coordinately integrate CD44 ligation and integrin activation, circumventing chemokine-mediated signaling, yielding a step 2-bypass pathway of the canonical multistep paradigm of cell migration.
    Proceedings of the National Academy of Sciences 02/2011; 108(6):2258-63. DOI:10.1073/pnas.1018064108 · 9.81 Impact Factor
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    Robert Sackstein
    Blood 06/2010; 115(23):4626-7. DOI:10.1182/blood-2010-03-272955 · 10.43 Impact Factor
  • Robert Sackstein
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    ABSTRACT: The success of stem-cell-based regenerative therapeutics critically hinges on delivering relevant stem/progenitor cells to sites of tissue injury. To achieve adequate parenchymal infiltration following intravascular administration, it is first necessary that circulating cells bind to target tissue endothelium with sufficient strength to overcome the prevailing forces of hemodynamic shear. The principal mediators of these shear-resistant binding interactions consist of a family of C-type lectins known as "selectins" that bind discrete sialofucosylated glycans on their respective ligands. One member of this family, E-selectin, is an endothelial molecule that is inducibly expressed on postcapillary venules at all sites of tissue injury, but is also constitutively expressed on the luminal surface of bone marrow and dermal microvascular endothelium. Most stem/progenitor cells express high levels of CD44, and, in particular, human hematopoietic stem cells express a specialized sialofucosylated glycoform of CD44 known as "hematopoietic cell E-/L-selectin ligand" (HCELL) that functions as a potent E-selectin ligand. This chapter describes a method called "glycosyltransferase-programmed stereosubstitution" (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells that natively lack HCELL. Ex vivo glycan engineering of HCELL via GPS licenses trafficking of infused cells to endothelial beds that express E-selectin, thereby enabling efficient vascular delivery of stem/progenitor cells to sites where they are needed.
    Methods in enzymology 01/2010; 479:93-105. DOI:10.1016/S0076-6879(10)79005-4 · 2.19 Impact Factor
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    Ronald Chester · Robert Sackstein
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    ABSTRACT: The breakneck speed of scientific developments in embryonic stem (ES) cell technologies is, commensurately, ushering forth new bioethical debate(s) regarding these cells. A framework of bioethical principles is presented here to guide biomedical scientists and others engaged in improving human welfare through the application of ES cell-based therapies.
    Health matrix 01/2010; 20(1):203-17.
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    ABSTRACT: A number of glycosyltransferases are present in human plasma with the (13) fucosyltransferase, Fucosyltransferase VI (FTVI), having the highest plasma concentration. Notably, elevated plasma levels of FTVI are associated with a variety of cancers and correlate with tumor load/progression. The well-known association of neoplasia with thromboembolic complications prompted us to examine whether FTVI has direct effect(s) on platelet function. We obtained human platelets from blood of healthy donors and separated from platelet-rich plasma by differential centrifugation. Freshly isolated platelets (x108/ml) were stirred and exposed at 37°C to varying concentrations (20, 40, 60 and 80 mU/mL) of glycosyltransferases FTVI, β-1-4-galactosyltransferase-I (βGalT-I), or ,2-3-N-sialyltransferase (2,3-N-ST), or to 1 U/mL thrombin. Platelet aggregation and activation was assessed by aggregometry (light transmission) or by flow cytometry of FSC/SSC characteristics and of surface expression of P-Selectin, respectively. FT-VI reproducibly induced platelet aggregation and activation, whereas other glycosyltransferases (β4GalT-I and 2,3-N-ST) had no effect on platelets. FTVI activation of platelets was concentration-dependent, and the aggregation curve for FTVI was one wave, similar to that for thrombin. FTVI-induced platelet activation was independent of catalytic conversion of surface glycans, but was inhibited by FTVI denaturation, indicating that FTVI-induced platelet activation is a lectin-mediated process. To determine the membrane target(s) mediating FTVI-induced platelet activation, biochemical studies were performed after catalytic exofucosylation of the platelet surface. Flow cytometry after platelet exofucosylation showed formation of the carbohydrate structure sLex, detected by the mAb Heca452, but no formation of Lex (CD15). Western blot showed that enforced fucosylation induced sLex on a single platelet surface protein, and further biochemical studies revealed that this protein is GPIb. These findings unveil a previously unrecognized property of FTVI as an activator of platelets, mediated via a specific lectin/carbohydrate interaction on GP1ba, and offer novel perspectives on the pathobiology of tumor-associated thrombogenesis.
    Blood 11/2009; 114(22):4016. · 10.43 Impact Factor

Publication Stats

4k Citations
644.38 Total Impact Points

Institutions

  • 2004–2015
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
    • University of South Florida
      Tampa, Florida, United States
  • 2001–2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1984–2014
    • Harvard Medical School
      • • Department of Dermatology
      • • Department of Medicine
      • • Department of Pediatrics
      Boston, Massachusetts, United States
    • Boston Children's Hospital
      • Department of Pediatrics
      Boston, Massachusetts, United States
  • 2004–2012
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, Massachusetts, United States
  • 1999–2002
    • Massachusetts General Hospital
      • • Transplantation Biology Research Center
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 1994–1997
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 1988
    • University of Miami
      • Department of Medicine
      كورال غيبلز، فلوريدا, Florida, United States