The heart wall tissue, or the myocardium, is one of the main targets in cardiovascular disease prevention and treatment. Animal models have not been sufficient in mimicking the human myocardium as evident by the very low clinical translation rates of cardiovascular drugs. Additionally, current models of the human myocardium possess several shortcomings such as lack of physiologically relevant co-culture of myocardial cells, lack of a 3D biomimetic environment, and the use of non-human cells. In this study, we address these shortcomings through the design and manufacture of a myocardium-on-chip (MOC) using 3D cell-laden hydrogel constructs and human induced pluripotent stem cell (hiPSC) derived myocardial cells. The MOC utilizes 3D spatially controlled co-culture of hiPSC derived cardiomyocytes (iCMs) and hiPSC derived endothelial cells (iECs) integrated among iCMs as well as in capillary-like side channels, to better mimic the microvasculature seen in native myocardium. We first fully characterized iCMs using immunostaining, genetic, and electrochemical analysis and iECs through immunostaining and alignment analysis to ensure their functionality, and then seeded these cells sequentially into the MOC device. We showed that iECs could be cultured within the microfluidic device without losing their phenotypic lineage commitment, and align with the flow upon physiological level shear stresses. We were able to incorporate iCMs within the device in a spatially controlled manner with the help of photocrosslinkable polymers. The iCMs were shown to be viable and functional within the device up to 7 days, and were integrated with the iECs. The iCMs and iECs in this study were derived from the same hiPSC cell line, essentially mimicking the myocardium of an individual human patient. Such devices are essential for personalized medicine studies where the individual drug response of patients with different genetic backgrounds can be tested in a physiologically relevant manner.
An ultra-bright extracellular optical field probe enabling label-free detection of electrogenic activity is introduced.
Lung disorders such as chronic obstructive pulmonary disease (COPD) and lower respiratory tract infections (LRTIs) are leading causes of death in humans globally. Cigarette smoking is the principal risk factor for the development of COPD, and LRTIs are caused by inhaling respiratory pathogens. Thus, a thorough understanding of host-environment/pathogen interactions is crucial to developing effective preventive and therapeutic modalities against these disorders. While animal models of human pulmonary conditions have been widely utilized, they suffer major drawbacks due to inter-species differences, hindering clinical translation. Here we summarize recent advances in generating complex 3D culture systems that emulate the microarchitecture and pathophysiology of the human lung, and how these platforms have been implemented for studying exposure to environmental factors, airborne pathogens, and therapeutic agents.
Conventional complementary metal oxide semiconductor (CMOS) transistors working in the Boolean paradigm and guided by Moore's law constitute the backbone of our current computational framework. However, certain classes of computational problems are fundamentally difficult to solve in the Boolean framework. Constrained optimization problems like vertex coloring of graphs, which is the task of assigning colors to the vertices of the graph such that no two vertices sharing the same edge have the same color, belong to the class of combinatorial optimization problems. [1] Such compute tasks find extensive applications in many real-world problems such as fault diagnosis, scheduling, and resource allocation. However, these problems fundamentally exhibit NP-hard (nondeterministic polynomial time) complexity. This implies that even the best algorithms end up searching the vast solution space in a greedy fashion for certain problem instances. Consequently, this manifests itself as an exponential increase in solution-time and computational resource with increasing size of the problem, when solved in the conventional Boolean computing framework. In contrast to the inherently sequential approach of digital CMOS which takes incremental discrete steps following the algorithm as the computation proceeds, the computational properties of the coupled oscillators arise from their rich spatiotemporal dynamics that enables the system to search in a highly parallel fashion, the high-dimensional configuration space that characterizes combinatorial optimization problems, and the driven by the dynamics synchronization drives the continuous time trajectory to settle at or close to the global minima.Biological systems have been inspiring many approaches that aim to build new computing modules using synthetic biology. [2,3] Most of the research so far in this area aims to create data storage or basic logic units that are built by engineering the genetic elements of single cells, including bacteria and mammalian cells. [4]
Heart transplantation is a life-saving therapy for end-stage organ failure. Organ deterioration during transportation limits storage to 4 hours, limiting hearts available. Approaches ameliorating organ damage could increase the number of hearts acceptable for transplantation. Prior studies show that adipose-derived stem/stromal cell secretome (ASC-S) rescues tissues from postischemic damage in vivo. This study tested whether ASC-S preserved the function of mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes (iCM) exposed to organ transportation and transplantation conditions. Hearts were subjected to cold University of Wisconsin (UW) cardioplegic solution ± ASC-S for 6 hours followed by analysis using the Langendorff technique. In parallel, the effects of ASC-S on the recovery of iCM from UW solution were examined when provided either during or after cold cardioplegia. Exposure of hearts and iCM to UW deteriorated contractile activity and caused cell apoptosis, worsening in iCM as a function of exposure time; these were ameliorated by augmenting with ASC-S. Silencing of superoxide dismutase 3 and catalase expression prior to secretome generation compromised the ASC-S cardiomyocyte-protective effects. In this study, a novel in vitro iCM model was developed to complement a rodent heart model in assessing efficacy of approaches to improve cardiac preservation. ASC-S displays strong cardioprotective activity on iCM either with or following cold cardioplegia. This effect is associated with ASC-S-mediated cellular clearance of reactive oxygen species. The effect of ASC-S on the temporal recovery of iCM function supports the possibility of lengthening heart storage by augmenting cardioplegic transport solution with ASC-S, expanding the pool of hearts for transplantation.
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