Human-derived decellularized extracellular matrix scaffold incorporating autologous bone marrow stem cells from patients with congenital heart disease for cardiac tissue engineering

Article type: Research Article

Authors: Gao, Liping^{a; b; ;} | Li, Xuexia^c; | Tan, Rubin^{a; b} | Cui, Jie^{a; b} | Schmull, Sebastian^d

Affiliations: [a] Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, China | [b] National Demonstration Center for Experiment Basic Medical Science Education, Xuzhou Medical University, Xuzhou, Jiangsu, China | [c] Department of Endocrinology, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, China | [d] Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Correspondence: [*] Corresponding author: Liping Gao, PhD, Department of Physiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, China. Tel.: +86 516 83262618; Fax: +86 516 83262858. E-mail: [email protected]

Note: [†] Liping Gao and Xuexia Li contributed equally to this work and should be considered co-first authors.

Abstract: BACKGROUND:Stem cells are used as an alternative treatment option for patients with congenital heart disease (CHD) due to their regenerative potential, but they are subject to low retention rate in the injured myocardium. Also, the diseased microenvironment in the injured myocardium may not provide healthy cues for optimal stem cell function. OBJECTIVE:In this study, we prepared a novel human-derived cardiac scaffold to improve the functional behaviors of stem cells. METHODS:Decellularized extracellular matrix (ECM) scaffolds were fabricated by removing cells of human-derived cardiac appendage tissues. Then, bone marrow c-kit+ progenitor cells from patients with congenital heart disease were seeded on the cardiac ECM scaffolds. Cell adhesion, survival, proliferation and cardiac differentiation on human cardiac decellularized ECM scaffold were evaluated in vitro. Label-free mass spectrometry was applied to analyze cardiac ECM proteins regulating cell behaviors. RESULTS:It was shown that cardiac ECM scaffolds promoted stem cell adhesion and proliferation. Importantly, bone marrow c-kit+ progenitor cells cultured on cardiac ECM scaffold for 14 days differentiated into cardiomyocyte-like cells without supplement with any inducible factors, as confirmed by the increased protein level of Gata4 and upregulated gene levels of Gata4, Nkx2.5, and cTnT. Proteomic analysis showed the proteins in cardiac ECM functioned in multiple biological activities, including regulation of cell proliferation, regulation of cell differentiation, and cardiovascular system development. CONCLUSION:The human-derived cardiac scaffold constructed in this study may help repair the damaged myocardium and hold great potential for tissue engineering application in pediatric patients with CHD.

Keywords: Extracellular matrix (ECM), c-kit, cardiac differentiation, tissue engineering, congenital heart disease

DOI: 10.3233/BME-211368

Journal: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 407-421, 2022