Evidence map›Paper›PMID 25149047›Full record

ArticleThe Annals of thoracic surgery2014

Enhanced lung epithelial specification of human induced pluripotent stem cells on decellularized lung matrix.

Sarah E Gilpin, Xi Ren, Tatsuya Okamoto, Jacques P Guyette, Hongmei Mou, Jayaraj Rajagopal, Douglas J Mathisen, Joseph P Vacanti, Harald C Ott

Abstract readComparative Study
In one paragraph

Article in The Annals of thoracic surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
12.6field-weighted citation impact, top 1% 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

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

  1. Pooled it
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  12. Lung Tissue Engineering: Toward a More Deliberate Approach.ACS biomaterials science & engineering · 2022
    Review
  13. Article
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  15. Lung Organoids-The Ultimate Tool to Dissect Pulmonary Diseases?Frontiers in cell and developmental biology · 2022
    Review
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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

9 authors at 2 institutions in 1 country.

Sarah E GilpinDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Xi RenDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Tatsuya OkamotoDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Jacques P GuyetteDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Hongmei MouDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Jayaraj RajagopalDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Douglas J MathisenDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Joseph P VacantiDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
Harald C OttDepartment of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. Electronic address: hott@partners.org.
Harvard University · USMassachusetts General Hospital · US

Funding

Bioengineering of Transplantable Humanized Lungs from iPS CellsR01HL108678 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N., VACANTI, JOSEPH P · 2011 to 2014
$2.8M
Organ engineering based on perfusion decellularized matrixDP2OD008749 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI OTT, HARALD C · 2011 to 2011
$2.6M
NHLBI NIH HHS 5R01-HL-108678-03NHLBI NIH HHS R01 HL108678NIH HHS DP2 OD008749NIH HHS DP2-OD008749-01
6 · The paper itself

Abstract

backgroundWhole-lung scaffolds can be created by perfusion decellularization of cadaveric donor lungs. The resulting matrices can then be recellularized to regenerate functional organs. This study evaluated the capacity of acellular lung scaffolds to support recellularization with lung progenitors derived from human induced pluripotent stem cells (iPSCs).

methodsWhole rat and human lungs were decellularized by constant-pressure perfusion with 0.1% sodium dodecyl sulfate solution. Resulting lung scaffolds were cryosectioned into slices or left intact. Human iPSCs were differentiated to definitive endoderm, anteriorized to a foregut fate, and then ventralized to a population expressing NK2 homeobox 1 (Nkx2.1). Cells were seeded onto slices and whole lungs, which were maintained under constant perfusion biomimetic culture. Lineage specification was assessed by quantitative polymerase chain reaction and immunofluorescent staining. Regenerated left lungs were transplanted in an orthotopic position.

resultsActivin-A treatment, followed by transforming growth factor-β inhibition, induced differentiation of human iPSCs to anterior foregut endoderm as confirmed by forkhead box protein A2 (FOXA2), SRY (Sex Determining Region Y)-Box 17 (SOX17), and SOX2 expression. Cells cultured on decellularized lung slices demonstrated proliferation and lineage commitment after 5 days. Cells expressing Nkx2.1 were identified at 40% to 60% efficiency. Within whole-lung scaffolds and under perfusion culture, cells further upregulated Nkx2.1 expression. After orthotopic transplantation, grafts were perfused and ventilated by host vasculature and airways.

conclusionsDecellularized lung matrix supports the culture and lineage commitment of human iPSC-derived lung progenitor cells. Whole-organ scaffolds and biomimetic culture enable coseeding of iPSC-derived endothelial and epithelial progenitors and enhance early lung fate. Orthotopic transplantation may enable further in vivo graft maturation.

Indexed as

Bioartificial OrgansTissue ScaffoldsAnimalsCadaverCell DifferentiationCells, CulturedEpithelial CellsExtracellular MatrixGraft SurvivalHumansInduced Pluripotent Stem CellsLungLung TransplantationRatsRats, Sprague-Dawley

Identifiers

PMID25149047
PMCPMC4252658
OpenAlexW2150862103

What OpenQuestion holds

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LicenceTDM
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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.