Evidence map›Paper›PMID 27723741›Full record

ArticleNature2016

Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.

Yuji Shiba, Toshihito Gomibuchi, Tatsuichiro Seto, Yuko Wada, Hajime Ichimura, Yuki Tanaka, Tatsuki Ogasawara, Kenji Okada, Naoko Shiba, Kengo Sakamoto and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 449 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
449citing papers in PubMed, 2 pooled it
40.0field-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

449 citing papers in PubMed, 2 syntheses or guidelines pooled it, 831 citations in OpenAlex.

  1. Pooled it
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  12. Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026
    Review
  13. Article
  14. Circumferential strain recovery after human cardiomyocyte transplantation in minipigs using a novel frequency-based method for myocardial tagging quantification.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2026
    Article
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389 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 1 country.

Yuji ShibaInstitute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan.
Toshihito GomibuchiDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Tatsuichiro SetoDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Yuko WadaDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Hajime IchimuraDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Yuki TanakaDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Tatsuki OgasawaraDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Kenji OkadaDepartment of Cardiovascular Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Naoko ShibaDepartment of Pediatrics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Kengo SakamotoIna Research Inc., Ina 399-4501, Japan.
Daisuke IdoIna Research Inc., Ina 399-4501, Japan.
Takashi ShiinaDepartment of Molecular Life Science, Tokai University School of Medicine, Isehara 259-1193, Japan.
Masamichi OhkuraBrain Science Institute, Saitama University, Saitama 338-8570, Japan.
Junichi NakaiBrain Science Institute, Saitama University, Saitama 338-8570, Japan.
Narumi UnoChromosome Engineering Research Center, Tottori University, Yonago 683-8503, Japan.
Yasuhiro KazukiChromosome Engineering Research Center, Tottori University, Yonago 683-8503, Japan.
Mitsuo OshimuraChromosome Engineering Research Center, Tottori University, Yonago 683-8503, Japan.
Itsunari MinamiInstitute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
Uichi IkedaDepartment of Cardiovascular Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Shinshu University · JPTottori University · JPSaitama University · JPKyoto University · JPTokai University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7.09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary.

Indexed as

AnimalsCell DifferentiationCell SurvivalFemaleFibroblastsGraft SurvivalHaplotypesHeartImmunosuppressive AgentsInduced Pluripotent Stem CellsMacaca fascicularisMajor Histocompatibility ComplexMaleMyocardial ContractionMyocardial InfarctionMyocytes, CardiacImmunosuppressive Agents

Identifiers

PMID27723741
OpenAlexW2528173482

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.