Engineered heart muscle allografts for heart repair in primates and humans.

Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques.

Pulmonary arterial banding in mice may be a suitable model for studies on ventricular mechanics in pediatric pulmonary arterial hypertension.

Background: The role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact of maintained pressure overload in the RV-pulmonary artery (PA) axis on myocardial strain and left ventricular (LV) mechanics in pediatric PAH patients in comparison to a preclinical PA-banding (PAB) mouse model. We hypothesize that the PAB mouse model mimics important aspects of interventricular mechanics of pediatric PAH and may be beneficial as a surrogate model for some longitudinal and interventional studies not possible in children.

Improving Right Ventricular Function by Increasing BMP Signaling with FK506.

Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation of BMP (bone morphogenetic protein) signaling with FK506 (tacrolimus) improved RV function by decreasing RV afterload. FK506 therapy further stabilized three patients with end-stage PAH.

Method for selective ablation of undifferentiated human pluripotent stem cell populations for cell-based therapies.

Human pluripotent stem cells (PSCs), which are composed of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an opportunity to advance cardiac cell therapy-based clinical trials. However, an important hurdle that must be overcome is the risk of teratoma formation after cell transplantation due to the proliferative capacity of residual undifferentiated PSCs in differentiation batches. To tackle this problem, we propose the use of a minimal noncardiotoxic doxorubicin dose as a purifying agent to selectively target rapidly proliferating stem cells for cell death, which will provide a purer population of terminally differentiated cardiomyocytes before cell transplantation.

Image-level supervised segmentation for human organs with confidence cues.

Image segmentation for human organs is an important task for the diagnosis and treatment of diseases. Current deep learning-based methods are fully supervised and need pixel-level labels. Since the medical images are highly specialized and complex, the work of delineating pixel-level segmentation masks is very time-consuming.

Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates.

Transposable elements (TEs) comprise nearly half of the human genome and are often transcribed or exhibit cis-regulatory properties with unknown function in specific processes such as heart development. In the case of endogenous retroviruses (ERVs), a TE subclass, experimental interrogation is constrained as many are primate-specific or human-specific. Here, we use primate pluripotent stem-cell-derived cardiomyocytes that mimic fetal cardiomyocytes in vitro to discover hundreds of ERV transcripts from the primate-specific MER41 family, some of which are regulated by the cardiogenic transcription factor TBX5.

Modeling Secondary Iron Overload Cardiomyopathy with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Excessive iron accumulation in the heart causes iron overload cardiomyopathy (IOC), which initially presents as diastolic dysfunction and arrhythmia but progresses to systolic dysfunction and end-stage heart failure when left untreated. However, the mechanisms of iron-related cardiac injury and how iron accumulates in human cardiomyocytes are not well understood. Herein, using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we model IOC and screen for drugs to rescue the iron overload phenotypes.

The left ventricle undergoes biomechanical and gene expression changes in response to increased right ventricular pressure overload.

Pulmonary hypertension (PH) results in right ventricular (RV) pressure overload and eventual failure. Current research efforts have focused on the RV while overlooking the left ventricle (LV), which is responsible for mechanically assisting the RV during contraction. The objective of this study is to evaluate the biomechanical and gene expression changes occurring in the LV due to RV pressure overload in a mouse model.

Histopathology Feature Mining and Association with Hyperspectral Imaging for the Detection of Squamous Neoplasia.

Hyperspectral imaging (HSI) is a noninvasive optical modality that holds promise for early detection of tongue lesions. Spectral signatures generated by HSI contain important diagnostic information that can be used to predict the disease status of the examined biological tissue. However, the underlying pathophysiology for the spectral difference between normal and neoplastic tissue is not well understood.

An miRNA Delivery System for Restoring Infarcted Myocardium.

A major challenge in myocardial infarction (MI)-related heart failure treatment using microRNA is the efficient and sustainable delivery of miRNAs into myocardium to achieve functional improvement through stimulation of intrinsic myocardial restoration. In this study, we established an delivery system using polymeric nanoparticles to carry miRNA (miNPs) for localized delivery within a shear-thinning injectable hydrogel. The miNPs triggered proliferation of human embryonic stem cell-derived cardiomyocytes and endothelial cells (hESC-CMs and hESC-ECs) and promoted angiogenesis in hypoxic conditions, showing significantly lower cytotoxicity than Lipofectamine.

[Treatment strategy for flail foot with sensory disorder of spina bifida sequela in adult].

Objective: To summarize the main methods and comprehensive effects of limited surgery combined with external fixation for the treatment of flail foot with sensory disorder of spina bifida sequela in adult.

Method: The clinical data of 22 cases (30 feet) of the adult spina bifida sequela who suffered from flail foot with sensory disorder and treated by limited surgery combined with external fixation were retrospectively analysed between January 2005 and December 2015. There were 14 males and 8 females with an age of 8-38 years (mean, 21.

[Data analysis of 8 113 cases of limb deformities corrected by external fixation].

Objective: To analyze the data of external fixation instruments (including Ilizarov instruments) used by QIN Sihe orthopaedic surgical team in the treatment of limb deformities in the past 30 years, and to explore the indications for the application of modern external fixation techniques in the correction of limb deformities and individual device configuration selection strategy.

Methods: According to QIN Sihe orthopaedic surgical team, the use of external fixator between January 1988 and December 2017 was analyzed retrospectively. The total use of external fixation and the proportion of different external fixators were analyzed in gender, different operation time, different age, different parts, and different diseases.

Adaptive deep learning for head and neck cancer detection using hyperspectral imaging.

It can be challenging to detect tumor margins during surgery for complete resection. The purpose of this work is to develop a novel learning method that learns the difference between the tumor and benign tissue adaptively for cancer detection on hyperspectral images in an animal model. Specifically, an auto-encoder network is trained based on the wavelength bands on hyperspectral images to extract the deep information to create a pixel-wise prediction of cancerous and benign pixel.

Photoacoustic Imaging of Embryonic Stem Cell-Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles.

The last decade has seen impressive progress in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that makes them ideal tools to repair injured hearts. To achieve an optimal outcome, advanced molecular imaging methods are essential to accurately track these transplanted cells in the heart. Herein, we demonstrate for the first time that a class of photoacoustic nanoparticles (PANPs) incorporating semiconducting polymers (SPs) as contrast agents can be used in the photoacoustic imaging (PAI) of transplanted hESC-CMs in living mouse hearts.

Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction.

Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 10 NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9-14/group) at 4 days after 60-min coronary artery occlusion-reperfusion.

Detection and delineation of squamous neoplasia with hyperspectral imaging in a mouse model of tongue carcinogenesis.

Hyperspectral imaging (HSI) holds the potential for the noninvasive detection of cancers. Oral cancers are often diagnosed at a late stage when treatment is less effective and the mortality and morbidity rates are high. Early detection of oral cancer is, therefore, crucial in order to improve the clinical outcomes.

Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles.

Background: The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance after such treatments are plagued by relatively low detection ability. Since the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility.

Determining Cardiac Fiber Orientation Using FSL and Registered Ultrasound/DTI volumes.

Accurate extraction of cardiac fiber orientation from diffusion tensor imaging is important for determining heart structure and function. However, the acquisition of magnetic resonance (MR) diffusion tensor images is costly and time consuming. By comparison, cardiac ultrasound imaging is rapid and relatively inexpensive, but it lacks the capability to directly measure fiber orientations.

Quantitative Diagnosis of Tongue Cancer from Histological Images in an Animal Model.

We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing.

Hyperspectral Imaging of Neoplastic Progression in a Mouse Model of Oral Carcinogenesis.

Hyperspectral imaging (HSI) is an emerging modality for medical applications and holds great potential for noninvasive early detection of cancer. It has been reported that early cancer detection can improve the survival and quality of life of head and neck cancer patients. In this paper, we explored the possibility of differentiating between premalignant lesions and healthy tongue tissue using hyperspectral imaging in a chemical induced oral cancer animal model.

Estimation of Tissue Optical Parameters with Hyperspectral Imaging and Spectral Unmixing.

Early detection of oral cancer and its curable precursors can improve patient survival and quality of life. Hyperspectral imaging (HSI) holds the potential for noninvasive early detection of oral cancer. The quantification of tissue chromophores by spectral unmixing of hyperspectral images could provide insights for evaluating cancer progression.