Evidence map›Paper›PMID 34657336›Full record

ArticleXenotransplantation2021

Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.

Margaret R Connolly, Kasinath Kuravi, Lars Burdorf, Lori Sorrells, Benson Morrill, Arielle Cimeno, Todd Vaught, Amy Dandro, Selin Sendil, Zahra A Habibabady and 8 more

Open access · greenAbstract read
In one paragraph

Article in Xenotransplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  13. Review
  14. Complement, Coagulation, and Fibrinolysis: The Role of the Endothelium and Its Glycocalyx Layer in Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Review
  15. Review
  16. Review
  17. Article
  18. Pig heart and lung xenotransplantation: Present status.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 2 countries.

Margaret R ConnollyMassachusetts General Hospital, Center for Transplantation Sciences, Boston, Massachusetts, USA.ORCID 0000-0002-6736-6352
Kasinath KuraviRevivicor, Blacksburg, Virginia, USA.
Lars BurdorfMassachusetts General Hospital, Center for Transplantation Sciences, Boston, Massachusetts, USA.
Lori SorrellsRevivicor, Blacksburg, Virginia, USA.
Benson MorrillRevivicor, Blacksburg, Virginia, USA.
Arielle CimenoUniversity of Maryland School of Medicine, Baltimore, Maryland, USA.
Todd VaughtRevivicor, Blacksburg, Virginia, USA.
Amy DandroRevivicor, Blacksburg, Virginia, USA.
Selin SendilUniversity of Maryland School of Medicine, Baltimore, Maryland, USA.
Zahra A HabibabadyMassachusetts General Hospital, Center for Transplantation Sciences, Boston, Massachusetts, USA.
Jeffery MonahanRevivicor, Blacksburg, Virginia, USA.
Tiezheng LiUniversity of Maryland School of Medicine, Baltimore, Maryland, USA.
John LaMattinaUniversity of Maryland School of Medicine, Baltimore, Maryland, USA.
Willard EyestoneRevivicor, Blacksburg, Virginia, USA.
David AyaresRevivicor, Blacksburg, Virginia, USA.
Carol PhelpsRevivicor, Blacksburg, Virginia, USA.
Agnes M AzimzadehMassachusetts General Hospital, Center for Transplantation Sciences, Boston, Massachusetts, USA.
Richard N PiersonMassachusetts General Hospital, Center for Transplantation Sciences, Boston, Massachusetts, USA.
University of Maryland, Baltimore · USMassachusetts General Hospital · US

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2010 to 2024
$26.3M
Therapeutic assessment of synthetic heparin sulfates in transplantation modelsP01HL107152 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DESAI, UMESH RAMANLAL · 2011 to 2017
$15.8M
TRAINING IN TRANSPLANTATION BIOLOGYT32AI007529 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI MADSEN, JOREN C · 1998 to 2024
$6.4M
CRISPR-Modified Cardiac Xenograft TransplantationU01AI153612 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI PIERSON, RICHARD N · 2021 to 2024
$3.2M
Mechanisms of GalTKO Lung Xenograft InjuryU01AI066335 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI PIERSON, RICHARD N · 2005 to 2009
$2.4M
NHLBI NIH HHS P01 HL107152NIAID NIH HHS T32 AI007529NIAID NIH HHS U01 AI066335NIAID NIH HHS U01 AI153612NIAID NIH HHS U19 AI090959
6 · The paper itself

Abstract

The transplantation of organs across species offers the potential to solve the shortage of human organs. While activation of human platelets by human von Willebrand factor (vWF) requires vWF activation by shear stress, contact between human platelets and porcine vWF (pvWF) leads to spontaneous platelet adhesion and activation. This non-physiologic interaction may contribute to the thrombocytopenia and coagulation pathway dysregulation often associated with xenotransplantation of pig organs in nonhuman primates. Pigs genetically modified to decrease antibody and complement-dependent rejection (GTKO.hCD46) were engineered to express humanized pvWF (h*pvWF) by replacing a pvWF gene region that encodes the glycoprotein Ib-binding site with human cDNA orthologs. This modification corrected for non-physiologic human platelet aggregation on exposure to pig plasma, while preserving in vitro platelet activation by collagen. Organs from pigs with h*pvWF demonstrated reduced platelet sequestration during lung (p ≤ .01) and liver (p ≤ .038 within 4 h) perfusion ex vivo with human blood and after pig-to-baboon lung transplantation (p ≤ .007). Residual platelet sequestration and activation were not prevented by the blockade of canonical platelet adhesion pathways. The h*pvWF modification prevents physiologically inappropriate activation of human or baboon platelets by porcine vWF, addressing one cause of the thrombocytopenia and platelet activation observed with xenotransplantation.

Indexed as

Thrombocytopeniavon Willebrand FactorAnimalsBlood PlateletsPlatelet AggregationPlatelet Glycoprotein GPIb-IX ComplexSwineTransplantation, HeterologousPlatelet Glycoprotein GPIb-IX Complexvon Willebrand Factorgenetic engineeringlung transplantationpigplateletsvon Willebrand factor

Identifiers

PMID34657336
PMCPMC10266522
OpenAlexW3206481164

What OpenQuestion holds

Textmetadata
LicenceTDM
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.