Evidence map›Paper›PMID 39681154›Full record

ArticleActa biomaterialia2025

Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering.

Luke Batty, Jinkyu Park, Lingfeng Qin, Muhammad Riaz, Yuyao Lin, Zhen Xu, Xuefei Gao, Xin Li, Colleen Lopez, Wei Zhang and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta biomaterialia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

25 authors.

Luke BattyDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA; Department of Pathology, Yale University, New Haven, CT 06510, USA.
Jinkyu ParkDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA; Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-gil, Chuncheon-si, Gangwon-Do, 24252, South Korea.
Lingfeng QinDepartment of Surgery, Yale University, New Haven, CT 06520, USA.
Muhammad RiazDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Yuyao LinDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA; Department of Plastic, Aesthetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Zhen XuDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Xuefei GaoDepartment of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Xin LiDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Colleen LopezDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Wei ZhangDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Marie HoareauDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Meghan E FallonDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Yan HuangDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Hangqi LuoDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Jiesi LuoDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA.
Séverine MénoretCenter for Research in Transplantation and Translational Immunology UMR1064, INSERM, Nantes Université, Nantes, France; Nantes Université, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Nantes, France.
Peining LiDepartment of Genetics, Yale University, New Haven, CT 06519, USA.
Zhenting JiangDepartment of Earth & Planetary Sciences, Yale University, New Haven, CT 06511, USA.
Peter SmithDepartment of Comparative Medicine, Yale University, New Haven, CT 06520, USA.
David H SachsDepartment of Surgery, Columbia Center for Translational Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
George TellidesDepartment of Surgery, Yale University, New Haven, CT 06520, USA.
Ignacio AnegonCenter for Research in Transplantation and Translational Immunology UMR1064, INSERM, Nantes Université, Nantes, France; Nantes Université, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Nantes, France.
Jordan S PoberDepartment of Pathology, Yale University, New Haven, CT 06510, USA; Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
Pentao LiuSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Stem Cell and Regenerative Medicine Consortium, Pokfulam, Hong Kong, China.
Yibing QyangDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA; Department of Pathology, Yale University, New Haven, CT 06510, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA. Electronic address: yibing.qyang@yale.edu.

Funding

XENOGRAFT TOLERANCE THROUGH MIXED CHIMERISMP01AI045897 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Megan Sykes · 2000 to 2026
$71.9M
Readily Available Stem Cell-Based Vascular Grafts for Emergent Surgical CareR01HL150352 · NHLBI · YALE UNIVERSITY · PI QYANG, YIBING · 2020 to 2023
$2.8M
Human tissue-engineered blood vessels using induced pluripotent stem cellsR01HL116705 · NHLBI · YALE UNIVERSITY · PI QYANG, YIBING · 2013 to 2017
$2.0M
Readily Available Biological Conduits to Treat Single Ventricle DefectsR01HL171984 · NHLBI · YALE UNIVERSITY · PI Yibing Qyang · 2024 to 2026
$1.7M
Development of HLA engineered universal vascular grafts from human iPSCsR01HL155411 · NHLBI · YALE UNIVERSITY · PI QYANG, YIBING · 2021 to 2024
$1.7M
PRODUCING PIG INDUCED PLURIPOTENT STEM CELLS FOR CARDIOVASCULAR TISSUE ENGINEERINGF31HL149289 · NHLBI · YALE UNIVERSITY · PI BATTY, LUKE DANIEL · 2019 to 2021
$126k
NHLBI NIH HHS F31 HL149289NHLBI NIH HHS R01 HL116705NHLBI NIH HHS R01 HL150352NHLBI NIH HHS R01 HL155411NHLBI NIH HHS R01 HL171984NIAID NIH HHS P01 AI045897
6 · The paper itself

Abstract

Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of cardiovascular diseases through cell-based therapies, but these therapies require extensive preclinical testing that is best done in species-in-species experiments. Pigs are a good large animal model for these tests due to the similarity of their cardiovascular system to humans. However, a lack of adequate pig iPSCs (piPSCs) that are analogous to human iPSCs has greatly limited the potential usefulness of this model system. Herein, transgene-free piPSCs with true pluripotency were generated by using reprogramming factors in an optimized pig pluripotency medium. Using an effective differentiation protocol, piPSCs were used to derive endothelial cells (ECs) which displayed EC markers and functionality comparable to native pig ECs. Further, piPSC-ECs demonstrated suitability for vascular tissue engineering, producing a tissue engineered vascular conduit (TEVC) that displayed the upregulation of flow responding markers. In an in vivo functional study, these piPSC-EC-TEVCs maintained the expression of endothelial markers and prevented thrombosis as interposition inferior vena cava grafts in immunodeficient rats. The piPSCs described in this study open up the possibility of unique preclinical species-in-species large animal modeling for the furtherance of modeling of cell-based cardiovascular tissue engineering therapies. STATEMENT OF SIGNIFICANCE: While there has been significant progress in the development of cellularized cardiovascular tissue engineered therapeutics using stem cells, few of them have moved into clinical trials. This is due to the lack of a robust preclinical large animal model to address the high safety and efficacy standards for transplanted therapeutics. In this study, pig stem cells that are analagous to human's were created to address this bottleneck. They demonstrated the ability to differentiate into functional endothelial cells and were able to create a tissue engineered therapeutic that is analogous to a human therapy. With these cells, future experiments testing the safety and efficacy of tissue engineered constructs are possible, bringing these crucial therapeutics closer to the patients that need them.

Indexed as

Blood Vessel ProsthesisEndothelial CellsInduced Pluripotent Stem CellsTissue EngineeringTransgenesAnimalsCell DifferentiationHumansRatsSwineEndothelial cellsPig induced pluripotent stem cellsTissue engineeringTransgene-free

Identifiers

PMID39681154
PMCPMC12212065

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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.