Tissue-engineered cardiac patch seeded with human induced pluripotent stem cell derived cardiomyocytes promoted the regeneration of host cardiomyocytes in a rat model.

Tadahisa Sugiura,Christopher K Breuer,Narutoshi Hibino,Toshiharu Shinoka

doi:10.1186/s13019-016-0559-z

Tadahisa Sugiura, Christopher K Breuer + Show 2 more

Open Access

https://doi.org/10.1186/s13019-016-0559-z

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Abstract

BackgroundThousands 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.MethodsThe 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.ResultsSeeded 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.ConclusionsSeeded 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.

Highlights

Thousands of babies are born with congenital heart defects that require surgical repair involving a prosthetic implant
Induced pluripotent stem cells were first generated by nuclear reprogramming of mouse fibroblasts in 2006 [3], and human iPS cells were established in 2007 [4, 5]
Immunofluorescent staining for αactinin showed the human iPS (hiPS)-CMs were positive for αactinin and they were positive for red fluorescent protein (Fig. 1)

Summary

Introduction

Thousands of babies are born with congenital heart defects that require surgical repair involving a prosthetic implant. 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. Currently used prosthetic materials lack growth potential and they necessitate staged repairs or re-operations. These additional surgical procedures add additional morbidity because of increased complexity due to the formation of significant pericardial adhesions. A tissue-engineered graft is made up of a scaffold and seeded cells. Using the classical tissue engineering paradigm, many cell types have been considered as possibilities for seeding onto a biodegradable scaffold, which provides sites for cell attachment and space for neotissue formation [2]. Human iPS cells represent an unlimited source of cardiomyocytes because of their great potential for differentiation and are one of the most promising sources of cells for cardiac regeneration therapy [7, 8]

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