P148Cardiac myocytes are protected by small leucine rich proteoglycans against simulated ischemia/reperfusion injury

Gáspár, Renáta; Görbe, Anikó; Pálóczi, János; Varga, ZV; Gömöri, Kamilla; Ferdinándy, Péter; Csont, Tamás

doi:10.1093/cvr/cvu082.87

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“…Cells on PDMS-L started beating on the 6th day of initiation, whereas it took at least 7 days for cells on other surfaces. This enhanced effect of Leu-SAM-modified PDMS on cardiac specification can be explained by leucine-rich proteoglycans, which are one of the critical components of myocardial ECM. − In addition to the surface chemical composition, wettability is also an important surface characteristic for cellular behavior and its effects depend on the cell type. For example, hydrophobic culture environments were found to enable uniform embryoid body formation of ESCs, in addition to better viability and differentiation .…”

Section: Discussionmentioning

confidence: 99%

Impact of Poly(dimethylsiloxane) Surface Modification with Conventional and Amino Acid-Conjugated Self-Assembled Monolayers on the Differentiation of Induced Pluripotent Stem Cells into Cardiomyocytes

Öztürk-Öncel

Heras-Bautista

Uzun

et al. 2021

ACS Biomater. Sci. Eng.

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Cardiomyocytes, differentiated from induced pluripotent stem cells (iPSCs), have the potential to produce patient- and disease-specific pharmacological and toxicological platforms, in addition to their cardiac cell therapy applications. However, the lack of both a robust and a simple procedure for scalable cell substrate production is one of the major limitations in this area. Mimicking the natural healthy myocardium extracellular matrix (ECM) properties by altering the cell substrate properties, such as stiffness and chemical/biochemical composition, can significantly affect cell substrate interfacial characteristics and potentially influence cellular behavior and differentiation of iPSCs to cardiomyocytes. Here, we propose a systematic and biomimetic approach, based on the preparation of poly(dimethylsiloxane) (PDMS) substrates having the similar stiffness as healthy heart tissue and a well-defined surface chemistry obtained by conventional [(3-aminopropyl)triethoxysilane (APTES) and octadecyltrimethoxysilane (OTS)] and amino acid (histidine and leucine)-conjugated self-assembled monolayers (SAMs). Among a wide range of different concentrations, the 50:1 prepolymer cross-linker ratio of PDMS allowed adaptation of the myocardium stiffness with a Young’s modulus of 23.79 ± 0.61 kPa. Compared with conventional SAM modification, amino acid-conjugated SAMs greatly improved iPSC adhesion, viability, and cardiac marker expression by increasing surface biomimetic properties, whereas all SAMs enhanced cell behavior, with respect to native PDMS. Furthermore, leucine-conjugated SAM modification provided the best environment for cardiac differentiation of iPSCs. This optimized approach can be easily adapted for cardiac differentiation of iPSCs in vitro, rendering a very promising tool for microfluidics, drug screening, and organ-on-chip platforms.

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