Physiological aspects of cardiac tissue engineering

Abstract

Cardiac tissue engineering aims at repairing the diseased heart and developing cardiac tissues for basic research and predictive toxicology applications. Since the first description of engineered heart tissue 15 years ago, major development steps were directed toward these three goals. Technical innovations led to improved three-dimensional cardiac tissue structure and near physiological contractile force development. Automation and standardization allow medium throughput screening. Larger constructs composed of many small engineered heart tissues or stacked cell sheet tissues were tested for cardiac repair and were associated with functional improvements in rats. Whether these approaches can be simply transferred to larger animals or the human patients remains to be tested. The availability of an unrestricted human cardiac myocyte cell source from human embryonic stem cells or human-induced pluripotent stem cells is a major breakthrough. This review summarizes current tissue engineering techniques with their strengths and limitations and possible future applications.

Development of a human cardiac organoid injury model reveals innate regenerative potential

“…Recent advances in stem cell biology and tissue engineering have provided unprecedented access to human heart tissue for basic biological studies, disease modeling, drug screening and regenerative medicine applications (Eder et al, 2016;Eschenhagen et al, 2012). Robust protocols have been developed to differentiate human pluripotent stem cells (hPSC), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), to produce cardiomyocytes (Hudson and Zimmermann, 2011).…”

Cardiac Tissue Engineering

“…75 The lower forces in engineered cardiac constructs are mainly explained by lower cardiac myocyte density, lower sarcomere volume fraction, and the overall lower level of cardiac myocyte differentiation. 74 Cardiac 3D constructs from chickens, rats, mice, and humans show a positive inotropic and chronotropic response to β-adrenergic stimulation, which is sensitive to the muscarinic agonist carbachol. 74 Furthermore, they increase force with ; in rat, 76 murine, 22 and mouse EHTs, 77 it was negative.…”

“…74 Cardiac 3D constructs from chickens, rats, mice, and humans show a positive inotropic and chronotropic response to β-adrenergic stimulation, which is sensitive to the muscarinic agonist carbachol. 74 Furthermore, they increase force with ; in rat, 76 murine, 22 and mouse EHTs, 77 it was negative. Collectively, this demonstrates that 3D engineered tissues function qualitatively like native muscle.…”

Engineering Cardiovascular Regeneration

“…Since lentivirus randomly integrate into the host genome and may thereby activate or inactivate genes, many researchers worked on improving this method by using non-integrating viral transduction such as Sendai virus [43•], direct transfer of mRNA [44] or proteins [45], or replacing some of the pluripotency factors by small molecules [46,47]. Given the relative ease and robustness and the lack of ethical concerns in their generation, human iPSC (hiPSC) are becoming increasingly important not only in the field of regeneration [48] but also as an unlimited source of patient/ disease-specific differentiated cells with great economic potential (e.g., Axiogenesis AG, Cellular Dynamics International, Pluriomics).…”

“…Various systems have been developed to fix the remodeling tissue and provide the mechanical strain necessary for cell orientation between the fixation points. The setup ranges from Velcro-coated glass tubes [94], rings [95], Flexcell chambers [97], and mesoscopic micropost arrays [98] to newer systems in which the fixation posts serve as means to measure contractile force [99,100] (overview in [48]). For cardiac repair, the hydrogel systems can be upscaled, either by employing larger casting molds [101] or assembling of several smaller elements [102].…”