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Since an impaired coronary blood supply following myocardial infarction (MI) negatively affects heart function, therapeutic neovascularization is considered one of the major therapeutic strategies for cell-based cardiac repair. Here, to more effectively achieve therapeutic neovascularization in ischemic hearts, we developed a dual stem cell approach for effective vascular regeneration by utilizing two distinct types of stem cells, CD31+-endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) and engineered human mesenchymal stem cells that continuously secrete stromal derived factor-1α (SDF-eMSCs), to simultaneously promote natal vasculogenesis and angiogenesis, two core mechanisms of neovascularization. To induce more comprehensive vascular regeneration, we intramyocardially injected hiPSC-ECs to produce de novo vessels, possibly via vasculogenesis, and a 3D cardiac patch encapsulating SDF-eMSCs (SDF-eMSC-PA) to enhance angiogenesis through prolonged secretion of paracrine factors, including SDF-1α, was implanted into the epicardium of ischemic hearts. We verified that hiPSC-ECs directly contribute to de novo vessel formation in ischemic hearts, resulting in enhanced cardiac function. In addition, the concomitant implantation of SDF1α-eMSC-PAs substantially improved the survival, retention, and vasculogenic potential of hiPSC-ECs, ultimately achieving more comprehensive neovascularization in the MI hearts. Of note, the newly formed vessels through the dual stem cell approach were significantly larger and more functional than those formed by hiPSC-ECs alone. In conclusion, these results provide compelling evidence that our strategy for effective vascular regeneration can be an effective means to treat ischemic heart disease.

Monte Carlo Tree Search (MCTS) algorithms show outstanding strengths in decision-making problems such as the game of Go. However, MCTS requires significant computing loads to evaluate many nodes in the decision tree to make a good decision. Parallelizing MCTS node evaluations is challenging because MCTS is a sequential process that each round of tree traversal depends on the previous node evaluations. In this work, we present SpecMCTS, a new approach for accelerating MCTS by speculatively traversing the search tree. Many MCTS applications, such as AlphaGo Zero, use a deep neural network (DNN) model to evaluate the tree nodes during the search. SpecMCTS uses a pair of DNN models, the speculation model and the main model. The faster (but less accurate) speculation model accelerates the sequential tree search while the more accurate main model improves the decision quality. SpecMCTS accelerates MCTS for the game of Go by up to $2.09\times {}$ on the NVIDIA T4 GPU. This performance improvement can be translated into a better decision quality by performing a larger number of tree traversals within the time limit. For a fixed decision time, SpecMCTS shows stronger gameplay (higher win rate) than the original sequential MCTS and state-of-the-art MCTS parallelization approaches.

Recent advances in biofabrication techniques, including 3D bioprinting, have allowed for the fabrication of cardiac models that are similar to the human heart in terms of their structure (e.g., volumetric scale and anatomy) and function (e.g., contractile and electrical properties). The importance of developing techniques for assessing the characteristics of 3D cardiac substitutes in real time without damaging their structures has also been emphasized. In particular, the heart has two primary mechanisms for transporting blood through the body: contractility and an electrical system based on intra and extracellular calcium ion exchange. This review introduces recent trends in 3D bioprinted cardiac tissues and the measurement of their structural, contractile, and electrical properties in real time. Cardiac models have also been regarded as alternatives to animal models as drug-testing platforms. Thus, perspectives on the convergence of 3D bioprinted cardiac tissues and their assessment for use in drug development are also presented.

Tremendous advances have been made toward accurate recapitulation of the human intestinal system in vitro to understand its developmental process, and disease progression. However, current in vitro models are often confined to 2D or 2.5D microarchitectures, which is difficult to mimic the systemic level of complexity of the native tissue. To overcome this problem, we develop physiologically relevant intestinal models with a 3D hollow tubular structure using 3D bioprinting strategy. A tissue-specific biomaterial, colon-derived decellularized extracellular matrix (Colon dECM) has been developed and it provides significant maturation-guiding potential to human intestinal cells. To fabricate a perfusable tubular model, we develop a simultaneous printing process of multiple materials through concentrically assembled nozzles and employ a light-activated Colon dECM bioink by supplementing with ruthenium/sodium persulfate as a photoinitiator. The bioprinted intestinal tissue models show spontaneous 3D morphogenesis of the human intestinal epithelium without any external stimuli. In consequence, the printed cells form multicellular aggregates and cysts and then differentiate into several types of enterocytes, building junctional networks. This system can serve as a platform to evaluate the effects of potential drug-induced toxicity on the human intestinal tissue and create a co-culture model with commensal microbes and immune cells for future therapeutics. This article is protected by copyright. All rights reserved.