Novel xeno-free human heart matrix-derived three-dimensional scaffolds

Journal of Translational Medicine

Research

Francisco Silva¹  Dolly Holt-Casper¹  Jeff M Theisen¹  David A Bull²  Amit N Patel³  David W Grainger⁴  Alonso P Moreno⁵  Mark Warren⁵ 

[1] Division of Cardiothoracic Surgery, Department of Surgery, University of Utah, 84112, Salt Lake City, UT, USA;Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 84112, Salt Lake City, UT, USA;Division of Cardiothoracic Surgery, Department of Surgery, University of Utah, 84112, Salt Lake City, UT, USA;Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 84112-5000, Salt Lake City, UT, USA;Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 84112, Salt Lake City, UT, USA;Division of Cardiothoracic Surgery, Department of Surgery, University of Utah, 84112, Salt Lake City, UT, USA;Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 84112-5000, Salt Lake City, UT, USA;Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 84112, Salt Lake City, UT, USA;University of Utah, 30 N 1900 E SOM 3c127, 84132, Salt Lake City, UT, USA;Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 84112-5000, Salt Lake City, UT, USA;Department of Bioengineering, University of Utah, 84112, Salt Lake City, UT, USA;Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 84112, Salt Lake City, UT, USA;Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 84112-5000, Salt Lake City, UT, USA;Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 84112, Salt Lake City, UT, USA;

关键词: Scaffolds;    Regeneration;    Cellular transplantation;    Cardiac ischemia;    Cardiomyocytes;    Viability;    Tissue engineering;    Cell signaling;   

DOI  :  10.1186/s12967-015-0559-0

 received in 2015-04-15, accepted in 2015-06-02,  发布年份 2015

来源: Springer

【 摘 要 】

RationaleMyocardial infarction (MI) results in damaged heart tissue which can progress to severely reduce cardiac function, leading to death. Recent studies have injected dissociated, suspended cardiac cells into coronary arteries to restore function with limited results attributed to poor cell retention and cell death. Extracellular matrix (ECM) injected into damaged cardiac tissue sites show some promising effects. However, combined use of human cardiac ECM and cardiac cells may produce superior benefits to restore cardiac function.ObjectiveThis study was designed to assess use of new three-dimensional human heart ECM-derived scaffolds to serve as vehicles to deliver cardiac-derived cells directly to damaged heart tissue and improve cell retention at these sites while also providing biomechanical support and attracting host cell recruitment.Methods and ResultsECM-derived porous protein scaffolds were fabricated from human heart tissues. These scaffolds were designed to carry, actively promote and preserve cardiac cell phenotype, viability and functional retention in tissue sites. ECM scaffolds were optimized and were seeded with human cardiomyocytes, cultured and subsequently implanted ex vivo onto infarcted murine epicardium. Seeded human cardiomyocytes readily adhered to human cardiac-derived ECM scaffolds and maintained representative phenotypes including expression of cardiomyocyte-specific markers, and remained electrically synchronous within the scaffold in vitro. Ex vivo, cardiomyocyte-seeded ECM scaffolds spontaneously adhered and incorporated into murine ventricle.ConclusionsDecellularized human cardiac tissue-derived 3D ECM scaffolds are effective delivery vehicles for human cardiac cells to directly target ischemic heart tissue and warrant further studies to assess their therapeutic potential in restoring essential cardiac functions.

【 授权许可】

CC BY   
© Holt-Casper et al. 2015