title: Tissue-engineered cardiac patch seeded with human induced pluripotent stem cell derived cardiomyocytes promoted the regeneration of host cardiomyocytes in a rat model.
abstract: 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.
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Tadahisa
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Narutoshi
authors.initials: N
authors.lastname: Hibino
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA. toshiharu.shinoka@nationwidechildrens.org.|Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA. toshiharu.shinoka@nationwidechildrens.org.|Cardiovascular Tissue Engineering Program, Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children's Hospital, 700 Children's Drive, T2294, Columbus, OH, 43205, USA. toshiharu.shinoka@nationwidechildrens.org.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
mesh_terms: D020341:Absorbable Implants; D000185:Actinin / Q000032:analysis; D000818:Animals; D002208:Caproates; D004195:Disease Models, Animal; D005240:Feasibility Studies; D006330:Heart Defects, Congenital / Q000601:surgery*; D006352:Heart Ventricles / Q000737:chemistry / Q000601:surgery*; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D007783:Lactones; D008297:Male; D009206:Myocardium / Q000737:chemistry; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000637:transplantation*; D011100:Polyglycolic Acid; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D012038:Regeneration; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D002208:Caproates; D007783:Lactones; D000185:Actinin; D011100:Polyglycolic Acid; C121056:caprolactone
keywords: Biodegradable cardiac patch; Congenital heart disease; Induced pluripotent stem cell derived cardiomyocytes; Tissue engineering