Tissue-engineered cardiac patch seeded with human induced pluripotent stem cell derived cardiomyocytes promoted the regeneration of host cardiomyocytes in a rat model
Open accessAbstract
BACKGROUND: Thousands of babies are born with congenital heart defects that require surgical repair involving a prosthetic implant. Lack of growth in prosthetic grafts is especially detrimental in pediatric surgery. Cell seeded biodegradable tissue engineered grafts are a novel solution to this problem. The purpose of the present study is to evaluate the feasibility of seeding human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) onto a biodegradable cardiac patch. METHODS: The hiPS-CMs were cultured on a biodegradable patch composed of a polyglycolic acid (PGA) and a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) for 1 week. Male athymic rats were randomly divided into 2 groups of 10 animals each: 1. hiPS-CM seeded group, and 2. Unseeded group. After culture, the cardiac patch was implanted to repair a defect with a diameter of 2 mm created in the right ventricular outflow tract (RVOT) wall. Hearts were explanted at 4 (n = 2), 8 (n = 2), and 16 (n = 6) weeks after patch implantation. Explanted patches were assessed immunohistochemically. RESULTS: Seeded patch explants did not stain positive for α-actinin (marker of cardiomyocytes) at the 4 week time point, suggesting that the cultured hiPS-CMs evacuated the patch in the early phase of tissue remodeling. However, after 16 weeks implantation, the area fraction of positively stained α-actinin cells was significantly higher in the seeded group than in the unseeded group (Seeded group: 6.1 ± 2.8% vs. Unseeded group: 0.95 ± 0.50%, p = 0.004), suggesting cell seeding promoted regenerative proliferation of host cardiomyocytes. CONCLUSIONS: Seeded hiPS-CMs were not present in the patch after 4 weeks. However, we surmise that they influenced the regeneration of host cardiomyocytes via a paracrine mechanism. Tissue-engineered hiPS-CMs seeded cardiac patches warrant further investigation for use in the repair of congenital heart diseases.
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PGA-PLCL patch loaded with cardiomyocytes promotes healing of myocardial defect area and expresses more α-actin.
“The results showed that the PGA-PLCL patch loaded with cardiomyocytes could promote the healing of the myocardium defect area and express more α-actin [167].”
From Application of PLCL as a biodegradable polymer in biomedical engineering (2026) · cites this paper as [167]
The Methods describe a cardiomyocyte-seeded PGA-PLCL patch used to cover a rat cardiac defect, and the Results report more cardiomyocyte-marker-positive cells in seeded patches after 16 weeks. However, the marker measured was α-actinin, not α-actin; the Results also do not establish that the seeded patch improved overall defect healing compared with an unseeded patch. The supplied copy has section labels but no page numbers. (LLM, conf=0.88)
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- Authors
- Sugiura, T., Hibino, N., Breuer, C. K., & Shinoka, T.
- Affiliations
- Nationwide Children's Hospital (US)
- Corresponding author
- Shinoka, Toshiharu
- Venue
- Journal of Cardiothoracic Surgery
- Published
- 2016-12
- Volume
- 11
- Issue
- 1
- Pages
- 163-163
- ISSN
- 1749-8090 (ISSN-L)
- PMC
- PMC5131419
- OpenAlex
- W2559051246
- Cited by
- 53
- References
- 25
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 2 · 2020: 8 · 2019: 9 · 2018: 14 · 2017: 2
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cardiothoracic Surgery (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health (R01-HL098228)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- iPSC-derived cardiomyocytes, polyglycolic acid, congenital heart disease, paracrine signaling, cell seeding, pediatric cardiac surgery
- MeSH terms
- Actinin, Animals, Caproates, Disease Models, Animal, Feasibility Studies, Heart Defects, Congenital, Heart Ventricles, Humans, Lactones, Male, Myocardium, Polyglycolic Acid, Random Allocation, Rats, Nude, Regeneration, Absorbable Implants, Tissue Engineering, Myocytes, Cardiac, Rats, Tissue Scaffolds, Induced Pluripotent Stem Cells
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