Evidence map›Paper›PMID 37237658›Full record

ArticleBioengineering (Basel, Switzerland)2023

One Billion hiPSC-Cardiomyocytes: Upscaling Engineered Cardiac Tissues to Create High Cell Density Therapies for Clinical Translation in Heart Regeneration.

Kiera D Dwyer, Rajeev J Kant, Arvin H Soepriatna, Stephanie M Roser, Mark C Daley, Sharif A Sabe, Cynthia M Xu, Bum-Rak Choi, Frank W Sellke, Kareen L K Coulombe

Abstract read
In one paragraph

Article in Bioengineering (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Animal and cellular models of atrial fibrillation: a review.Frontiers in cardiovascular medicine · 2025
    Review
  7. Article
  8. Review
  9. Advances in cardiac tissue engineering and heart-on-a-chip.Journal of biomedical materials research. Part A · 2024
    Review
  10. Article
  11. Journal of tissue engineering
    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

10 authors.

Kiera D DwyerSchool of Engineering, Brown University Center for Biomedical Engineering, Providence, RI 02912, USA.
Rajeev J KantSchool of Engineering, Brown University Center for Biomedical Engineering, Providence, RI 02912, USA.ORCID 0000-0002-3067-5880
Arvin H SoepriatnaSchool of Engineering, Brown University Center for Biomedical Engineering, Providence, RI 02912, USA.ORCID 0000-0002-7756-1389
Stephanie M RoserSchool of Engineering, Brown University Center for Biomedical Engineering, Providence, RI 02912, USA.ORCID 0000-0002-8398-2278
Mark C DaleySchool of Engineering, Brown University Center for Biomedical Engineering, Providence, RI 02912, USA.ORCID 0000-0002-7236-5215
Sharif A SabeCardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.ORCID 0000-0002-8169-6753
Cynthia M XuCardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
Bum-Rak ChoiCardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.ORCID 0000-0001-7319-3219
Frank W SellkeCardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
Kareen L K CoulombeSchool of Engineering, Brown University Center for Biomedical Engineering, Providence, RI 02912, USA.

Funding

Uncoupling of IL-1 beta and VEGF-A Crosstalk Contributes to Impaired Arteriogenesis Response to Ischemia in Chronic Diabetes MellitusP20GM103652 · NIGMS · OCEAN STATE RESEARCH INSTITUTE, INC. · PI YAO, HONGWEI · 2013 to 2022
$21.3M
Effect of Cardioplegia and Cardiopulmonary Bypass on Coronary Microvascular ReactivityR01HL046716 · NHLBI · RHODE ISLAND HOSPITAL · PI SELLKE, FRANK W · 1997 to 2023
$8.5M
Trauma and Inflammation Research TrainingT32GM065085 · NIGMS · RHODE ISLAND HOSPITAL · PI Alfred Ayala · 2004 to 2026
$3.2M
Cardiovascular Surgery Research TrainingT32HL160517 · NHLBI · RHODE ISLAND HOSPITAL · PI Frank W Sellke · 2022 to 2026
$1.5M
Impact of Glycemic Control on Extracellular Vesicle-Mediated Angiogenesis in a Porcine Model of Chronic Myocardial Ischemia and Metabolic SyndromeF32HL160063 · NHLBI · RHODE ISLAND HOSPITAL · PI SABE, SHARIF A. · 2021 to 2022
$149k
NHLBI NIH HHS F32 HL160063NHLBI NIH HHS R01 HL046716NHLBI NIH HHS T32 HL160517NIGMS NIH HHS P20 GM103652NIGMS NIH HHS T32 GM065085
6 · The paper itself

Abstract

Despite the overwhelming use of cellularized therapeutics in cardiac regenerative engineering, approaches to biomanufacture engineered cardiac tissues (ECTs) at clinical scale remain limited. This study aims to evaluate the impact of critical biomanufacturing decisions-namely cell dose, hydrogel composition, and size-on ECT formation and function-through the lens of clinical translation. ECTs were fabricated by mixing human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) and human cardiac fibroblasts into a collagen hydrogel to engineer meso-(3 × 9 mm), macro- (8 × 12 mm), and mega-ECTs (65 × 75 mm). Meso-ECTs exhibited a hiPSC-CM dose-dependent response in structure and mechanics, with high-density ECTs displaying reduced elastic modulus, collagen organization, prestrain development, and active stress generation. Scaling up, cell-dense macro-ECTs were able to follow point stimulation pacing without arrhythmogenesis. Finally, we successfully fabricated a mega-ECT at clinical scale containing 1 billion hiPSC-CMs for implantation in a swine model of chronic myocardial ischemia to demonstrate the technical feasibility of biomanufacturing, surgical implantation, and engraftment. Through this iterative process, we define the impact of manufacturing variables on ECT formation and function as well as identify challenges that must still be overcome to successfully accelerate ECT clinical translation.

Indexed as

biomanufacturingcell-dense tissuecell/tissue transplantationengineered cardiac tissueengraftmentheart regenerationhiPSC-cardiomyocytesmyocardial infarctionscale uptissue engineering

Identifiers

PMID37237658
PMCPMC10215511

What OpenQuestion holds

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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.