Evidence map›Paper›PMID 25202142›Full record

ArticleBlood2014

Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning.

Borja Saez, Francesca Ferraro, Rushdia Z Yusuf, Colleen M Cook, Vionnie W C Yu, Ana Pardo-Saganta, Stephen M Sykes, Rahul Palchaudhuri, Amir Schajnovitz, Sutada Lotinun and 11 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 2 countries.

Borja SaezStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Francesca FerraroStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Rushdia Z YusufStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Colleen M CookStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Vionnie W C YuStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Ana Pardo-SagantaCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Stephen M SykesImmune Cell Development and Host Defense, Research Institute of Fox Chase Cancer Center, Philadelphia, PA;
Rahul PalchaudhuriStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Amir SchajnovitzStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Sutada LotinunDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA;
Stefania LymperiStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Simon Mendez-FerrerCardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain;
Raquel Del ToroCardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain;
Robyn DayStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA;
Radovan VasicStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA;
Sanket S AcharyaStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA;
Roland BaronDepartment of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA;
Charles P LinHarvard Stem Cell Institute, Cambridge, MA; Advanced Microscopy Program, Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Boston, MA;
Yu YamaguchiSanford-Burnham Medical Research Institute, La Jolla, CA;
Amy J WagersStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Harvard Stem Cell Institute, Cambridge, MA; Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA; and Howard Hughes Medical Institute, Cambridge, MA.
David T ScaddenStem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA;
Harvard University · USHarvard Stem Cell Institute · USMassachusetts General Hospital · USSpanish National Centre for Cardiovascular Research · ESFox Chase Cancer Center · USHoward Hughes Medical Institute · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
Microenvironmental control of progenitors in organ dysfunction and repairU01HL100402 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, CARLA F., SCADDEN, DAVID T · 2009 to 2015
$8.5M
MECHANISMS OF HEMATOPOIESIS IN AIDSR01HL044851 · NHLBI · NEW ENGLAND DEACONESS HOSPITAL · PI SCADDEN, DAVID T · 1991 to 2015
$7.7M
Heparan Sulfate in Skeletal Development and DiseasesR01AR055670 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YAMAGUCHI, YU · 2008 to 2018
$4.9M
Stem Cell Engagement of the NicheR01HL097794 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 2009 to 2012
$2.4M
Direct visualization and characterization of hypoxia in the bone marrowR01HL097748 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI LIN, CHARLES P. · 2009 to 2012
$2.3M
Foxo transcription factors are required for maintenance of acute myeloid leukemiaR00CA158461 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI SYKES, STEPHEN MATTHEW · 2012 to 2014
$641k
NCI NIH HHS R00 CA158461NHLBI NIH HHS HL044851NHLBI NIH HHS HL097748NHLBI NIH HHS HL099997NHLBI NIH HHS HL100402NHLBI NIH HHS HL97794NHLBI NIH HHS R01 HL044851NHLBI NIH HHS R01 HL097748NHLBI NIH HHS R01 HL097794NHLBI NIH HHS U01 HL099997NHLBI NIH HHS U01 HL100402NIAMS NIH HHS R01 AR055670
6 · The paper itself

Abstract

The glycosyltransferase gene, Ext1, is essential for heparan sulfate production. Induced deletion of Ext1 selectively in Mx1-expressing bone marrow (BM) stromal cells, a known population of skeletal stem/progenitor cells, in adult mice resulted in marked changes in hematopoietic stem and progenitor cell (HSPC) localization. HSPC egressed from BM to spleen after Ext1 deletion. This was associated with altered signaling in the stromal cells and with reduced vascular cell adhesion molecule 1 production by them. Further, pharmacologic inhibition of heparan sulfate mobilized qualitatively more potent and quantitatively more HSPC from the BM than granulocyte colony-stimulating factor alone, including in a setting of granulocyte colony-stimulating factor resistance. The reduced presence of endogenous HSPC after Ext1 deletion was associated with engraftment of transfused HSPC without any toxic conditioning of the host. Therefore, inhibiting heparan sulfate production may provide a means for avoiding the toxicities of radiation or chemotherapy in HSPC transplantation for nonmalignant conditions.

Indexed as

Transplantation ConditioningAnimalsAnticoagulantsBinding, CompetitiveDiabetes Mellitus, ExperimentalExostosin 1Granulocyte Colony-Stimulating FactorGreen Fluorescent ProteinsHematopoietic Stem Cell MobilizationHematopoietic Stem Cell TransplantationHeparan SulfateHeparinMaleMice, Inbred C57BLMice, TransgenicN-AcetylglucosaminyltransferasesAnticoagulantsExostosin 1Granulocyte Colony-Stimulating FactorGreen Fluorescent ProteinsHeparan SulfateHeparinN-AcetylglucosaminyltransferasesVascular Cell Adhesion Molecule-1

Identifiers

PMID25202142
PMCPMC4224192
OpenAlexW2031473795

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.