Evidence map›Paper›PMID 37732466›Full record

ArticleCirculation2023

Combined Treatment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-Human Primates.

Yu-Che Cheng, Marvin L Hsieh, Chen-Ju Lin, Cindy M C Chang, Ching-Ying Huang, Riley Puntney, Amy Wu Moy, Chien-Yu Ting, Darien Zhing Herr Chan, Martin W Nicholson and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
9.8field-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

46 citing papers in PubMed, 64 citations in OpenAlex.

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  6. 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
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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

21 authors at 7 institutions in 6 countries.

Yu-Che ChengInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Marvin L HsiehModel Organisms Research Core, Department of Medicine (M.L.H., C.M.C.C., T.A.H.), University of Wisconsin-Madison.
Chen-Ju LinInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Cindy M C ChangModel Organisms Research Core, Department of Medicine (M.L.H., C.M.C.C., T.A.H.), University of Wisconsin-Madison.
Ching-Ying HuangInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Riley PuntneyWisconsin National Primate Research Center (R.P., A.W.M., J.C., P.B., H.A.S.), University of Wisconsin-Madison.
Amy Wu MoyWisconsin National Primate Research Center (R.P., A.W.M., J.C., P.B., H.A.S.), University of Wisconsin-Madison.
Chien-Yu TingInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Darien Zhing Herr ChanInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Martin W NicholsonInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Po-Ju LinInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Hung-Chih ChenInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).
Gina C KimDepartment of Medicine and Stem Cell and Regenerative Medicine Center (G.C.K., J.Z., T.J.K., P.C.H.H.), University of Wisconsin-Madison.
Jianhua ZhangDepartment of Medicine and Stem Cell and Regenerative Medicine Center (G.C.K., J.Z., T.J.K., P.C.H.H.), University of Wisconsin-Madison.
Jennifer CoonenWisconsin National Primate Research Center (R.P., A.W.M., J.C., P.B., H.A.S.), University of Wisconsin-Madison.
Puja BasuWisconsin National Primate Research Center (R.P., A.W.M., J.C., P.B., H.A.S.), University of Wisconsin-Madison.ORCID 0000-0003-4051-7998
Heather A SimmonsWisconsin National Primate Research Center (R.P., A.W.M., J.C., P.B., H.A.S.), University of Wisconsin-Madison.ORCID 0000-0002-4862-7289
Yen-Wen LiuDivision of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Y.W.L.).
Timothy A HackerModel Organisms Research Core, Department of Medicine (M.L.H., C.M.C.C., T.A.H.), University of Wisconsin-Madison.
Timothy J KampDepartment of Medicine and Stem Cell and Regenerative Medicine Center (G.C.K., J.Z., T.J.K., P.C.H.H.), University of Wisconsin-Madison.ORCID 0000-0003-2103-7876
Patrick C H HsiehInstitute of Biomedical Sciences, Academia Sinica, Taiwan (Y.C.C., C.J.L., C.Y.H., C.Y.T., D.Z.H.C., M.W.N., P.J.L., H.C.C., P.C.H.H.).ORCID 0000-0002-8910-3596
Academia Sinica · TWUniversity of Wisconsin–Madison · USConcordia University Wisconsin · USInstitute for Stem Cell Biology and Regenerative Medicine · INInstitute of Biomedical Sciences, Academia Sinica · TWNational Cheng Kung University Hospital · TWNational Taiwan University · TW

Funding

WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Integrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7M
NCATS NIH HHS UL1 TR002373NHLBI NIH HHS U01 HL134764NIH HHS P51 OD011106
6 · The paper itself

Abstract

backgroundRemuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs.

methodsWe generated 3 lines of hiPSC-derived endothelial cells (ECs) and hiPSC-CMs from 3 independent donors and tested hiPSC-CM sarcomeric length, gap junction protein, and calcium-handling ability in coculture with ECs. Next, we examined the therapeutic effect of the cotransplantation of hiPSC-ECs and hiPSC-CMs in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice undergoing myocardial infarction (n≥4). Cardiac function was assessed by echocardiography, whereas arrhythmic events were recorded using 3-lead ECGs. We further used healthy non-human primates (n=4) with cell injection to study the cell engraftment, maturation, and integration of transplanted hiPSC-CMs, alone or along with hiPSC-ECs, by histological analysis. Last, we tested the cell therapy in ischemic reperfusion injury in non-human primates (n=4, 3, and 4 for EC+CM, CM, and control, respectively). Cardiac function was evaluated by echocardiography and cardiac MRI, whereas arrhythmic events were monitored by telemetric ECG recorders. Cell engraftment, angiogenesis, and host-graft integration of human grafts were also investigated.

resultsWe demonstrated that human iPSC-ECs promote the maturity and function of hiPSC-CMs in vitro and in vivo. When cocultured with ECs, CMs showed more mature phenotypes in cellular structure and function. In the mouse model, cotransplantation augmented the EC-accompanied vascularization in the grafts, promoted the maturity of CMs at the infarct area, and improved cardiac function after myocardial infarction. Furthermore, in non-human primates, transplantation of ECs and CMs significantly enhanced graft size and vasculature and improved cardiac function after ischemic reperfusion.

conclusionsThese results demonstrate the synergistic effect of combining iPSC-derived ECs and CMs for therapy in the postmyocardial infarction heart, enabling a promising strategy toward clinical translation.

Indexed as

Induced Pluripotent Stem CellsMyocardial InfarctionAnimalsCell DifferentiationEndothelial CellsHumansMammalsMiceMice, Inbred NODMice, SCIDMyocytes, CardiacPrimatesarrhythmias, cardiacguided tissue regenerationinduced pluripotent stem cellmodels, animal

Identifiers

PMID37732466
PMCPMC10683868
OpenAlexW4386910283

What OpenQuestion holds

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Registered trials

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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.