Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration

Autor: Shu-Ling Jiang, Richard D. Weisel, Kai Kang, Milica Radisic, Terrence M. Yau, Lu Sun, Ren-Ke Li, Yun Xiao, Lei Yang, Jian Guo, Shu-Hong Li, Jun Wu
Předmět:
Cardiac function curve
Pathology
medicine.medical_specialty
Angiogenesis
medicine.medical_treatment
Heart Ventricles
Basic fibroblast growth factor
Myocardial Infarction
Biocompatible Materials
030204 cardiovascular system & hematology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Tissue engineering
Medicine
Animals
Humans
Rejuvenation
cardiac patch
Cardiac Surgical Procedures
Cells
Cultured
030304 developmental biology
Aged
0303 health sciences
Tissue Engineering
Tissue Scaffolds
business.industry
Myocardium
Mesenchymal stem cell
Middle Aged
medicine.disease
VEGF
Rats
Vascular endothelial growth factor
Disease Models
Animal
Cytokine
chemistry
bFGF
Heart failure
Immunology
Cytokines
business
mesenchymal stromal cells
Cardiology and Cardiovascular Medicine
surgical ventricular restoration
Zdroj: Scopus-Elsevier
Popis: Objectives 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.
Databáze: OpenAIRE
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