Wolfe Jayne T, He Wei, Kim Min-Su, Liang Huan-Ling, Shradhanjali Akankshya, Jurkiewicz Hilda, Freudinger Bonnie P, Greene Andrew S, LaDisa John F, Tayebi Lobat, Mitchell Michael E, Tomita-Mitchell Aoy, Tefft Brandon J
Department of Biomedical Engineering, Medical College of Wisconsin & Marquette University, Milwaukee, WI, United States.
Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, United States.
Front Cardiovasc Med. 2023 May 24;10:1162731. doi: 10.3389/fcvm.2023.1162731. eCollection 2023.
Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies.
To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521.
Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including spontaneous contraction. Contraction remained consistent during 30 days of culture based on displacement measurements. Furthermore, tissue constructs demonstrated progressive maturation based on sarcomere structure and gene expression analysis. Gene expression analysis also revealed enhanced maturation in 3D constructs compared to 2D cell culture.
This combination of patient-derived cardiomyocytes and 3D-bioprinting represents a promising platform for studying congenital heart disease and evaluating individualized treatment strategies.
先天性心脏病是与出生缺陷相关的主要死因,每100例活产中就有1例受其影响。诱导多能干细胞技术使人们能够在体外研究患者来源的心肌细胞。为了研究该疾病并评估潜在的治疗策略,需要一种将这些细胞生物工程化为生理上精确的心脏组织模型的方法。
为实现这一目标,我们开发了一种方案,用于3D生物打印心脏组织构建体,该构建体由基于层粘连蛋白-521的水凝胶生物墨水内的患者来源的心肌细胞组成。
心肌细胞保持存活,并表现出适当的表型和功能,包括自发收缩。根据位移测量,在30天的培养过程中收缩保持一致。此外,基于肌节结构和基因表达分析,组织构建体显示出逐渐成熟。基因表达分析还显示,与二维细胞培养相比,三维构建体中的成熟度有所提高。
患者来源的心肌细胞与3D生物打印的这种结合,代表了一个用于研究先天性心脏病和评估个体化治疗策略的有前景的平台。