title: Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration.
abstract: OBJECTIVE
  This study investigated whether cytokine enhancement of a biodegradable patch could restore cardiac function after surgical ventricular restoration (SVR) even when seeded with cells from old donors.
  
  
  BACKGROUND
  SVR can partially restore heart size and improve function late after an extensive anterior myocardial infarction. However, 2 limitations include the stiff synthetic patch used and the limited healing of the infarct scar in aged patients.
  
  
  METHODS
  We covalently immobilized 2 proangiogenic cytokines (vascular endothelial growth factor and basic fibroblast growth factor) onto porous collagen scaffolds. We seeded human mesenchymal stromal cells from young (50.0 ± 8.0 years, N = 4) or old (74.5 ± 7.4 years, N = 4) donors into the scaffolds, with or without growth factors. The patches were characterized and used for SVR in a rat model of myocardial infarction. Cardiac function was assessed.
  
  
  RESULTS
  In vitro results showed that cells from old donors grew slower in the scaffolds. However, the presence of cytokines modulated the aging-related p16 gene and enhanced cell proliferation, converting the old cell phenotype to a young phenotype. In vivo studies showed that 28 days after SVR, patches seeded with cells from old donors did not induce functional recovery as well as patches seeded with young cells. However, cytokine-enhanced patches seeded with old cells exhibited preserved patch area, prolonged cell survival, and augmented angiogenesis, and rats implanted with these patches had better cardiac function. The patch became an elastic tissue, and the old cells were rejuvenated.
  
  
  CONCLUSIONS
  This sustained-release, cytokine-conjugated system provides a promising platform for engineering myocardial tissue for aged patients with heart failure.
authors.affiliation: Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Jiang
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Yau
authors.forename: Richard D
authors.initials: RD
authors.lastname: Weisel
authors.forename: Milica
authors.initials: M
authors.lastname: Radisic
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
mesh_terms: D000368:Aged; D000818:Animals; D001672:Biocompatible Materials; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000601:surgery*; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012060:Rejuvenation / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines