Wired for function: engineering structural maturation and electrical coupling in hiPSC- derived cardiomyocytes
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) have emerged as a promising platform for the development of novel cell replacement therapies in cardiac regenerative medicine. However, despite standardized differentiation protocols, hiPSC-CM retain an immature phenotype, exhibiting a substantial functional gap compared to adult cardiomyocytes. This is particularly evident in Ca2+ handling, a key determinant of contractile function and force modulation, where deficits may underlie the spontaneous contractile activity or automaticity, characteristic of immature cells. Our research aims to promote the cardiogenic maturation of hiPSC-CM in vitro. We demonstrate that both environmental culture conditions and targeted structural and molecular remodelling significantly contribute to enhanced intracellular Ca2+ dynamics and more efficient excitation–contraction (EC) coupling. Furthermore, the limited intercellular connectivity typically observed in multicellular hiPSC-CM preparations can be improved through optimization of growth conditions that more closely mimic the physiological cardiac environment. Collectively, we present a range of experimental strategies to promote the maturation of hiPSC-CM toward a phenotype that more closely resembles adult cardiomyocytes. These insights offer a deeper understanding of how environmental and structural factors influence cardiomyocyte biomechanics and may facilitate the clinical translation of hiPSC-CM for use in cardiac cell therapy.
Evolutionary insect venomics
With over a million documented species, insects represent the most successful group of organisms in terms of biodiversity. At least 14 groups have independently evolved the use of venoms, which are poisonous secretions often delivered through specialized piercing mouthparts or stingers. Venoms can be used to immobilize and kill prey or for defense against predators and pathogens. The recent progress in the exploration of insect venoms as a valuable bioresource for toxins with potential for applications in medicine and agriculture was driven by the combined application of genomic, transcriptomic, proteomic and bioinformatic approaches (Venomics). The detailed molecular analysis of venoms even from small insects pathed the way to address evolutionary questions such as the adaptation of the toxins to different preys and ecological niches as well as the reconstruction of their functional shifts. The combination of venomics with modern microscopic and imaging methods facilitated pioneering studies on the evolution of venom glands and venom delivery structures. The presentation highlights current insights into the role of venoms in the evolution of ants, ant lions, true bugs, parasitic wasps and bombardier beetles.
