Abstract: Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

Abstract: Novel therapeutic protocols are provided relating to the use of an anti-IL-6 antibody, e.g., Clazakizumab, in order to prevent, stabilize, reduce or arrest antibody mediated rejection responses in patients receiving solid organ transplants, e.g., patients receiving transplanted kidney, heart, liver, lungs, pancreas, intestines or combinations of any of the foregoing. Also novel therapeutic protocols are provided pertaining to the use of an anti-IL-6 antibody, e.g., Clazakizumab, as part of a desensitization protocol for treating highly sensitized subjects waiting for and/or after allograft transplants, e.g., patients who are to receive solid organ transplants, e.g., kidney, heart, liver, lungs, pancreas, intestines, skin or combinations of any of the foregoing. The foregoing treatments may be effected in combination with one or more other immunosuppressant regimens or other desensitization procedures.

Abstract: The invention of the present disclosure relates to methods for diagnosing and for treating a progressive lung disease in a subject. In various embodiments, the method for treating a progressive lung disease in a subject includes administering a pharmaceutical composition comprising a Human Epidermal Growth Factor Receptor 2 (HER2) blocking agent and a pharmaceutically acceptable carrier to the subject, wherein the method improves clinical outcome compared to an untreated control.

Abstract: We combined single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without neoadjuvant chemotherapy (NAC), whereas CDH12-enriched tumors have a superior response to immune checkpoint therapy (ICT). Patient stratification by tumor CDH12 enrichment offered better prediction outcome than established bladder cancer subtypes. The CDH12 population resembles an undifferentiated state with chemoresistance. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), likely explaining ICT efficacy in these tumors.

Abstract: Diabetes is a clinical condition that affects millions of people worldwide, and is treated by insulin replacement therapies. New strategies to create scalable and compatible pancreatic islets containing insulin-producing beta cells are necessary as an alternative to limited supply of cadaveric islets or multiple exogenous insulin applications. Improvements are still necessary since many immature polyhormonal cells remain, and cannot attain a monohormonal state. During human development, pancreas co-develops with endothelium and shares signals, allowing for better maturation of beta cells, and this is not included in the current differentiation protocols. The organchip microfluidic devices allows dynamic co-culture of different cells, thus resembling in vivo physiology. Here the Inventors establish organ-chip models co-culturing human iPSC-derived pancreatic precursors with iPSC-derived endothelial cells to obtain more functional and monohormonal iPSC-derived beta cells.

Abstract: Systems and methods are disclosed for applying attenuation correction to single photon emission computed tomography (SPECT) imaging data for myocardial perfusion imaging (MPI) studies. SPECT-MPI imaging data can be provided to a deep-learning model to automatically generate simulated computed tomography attenuation correction (CT-AC) images from the non-corrected (NC) SPECT-MPI imaging data. These simulated CT-AC images can then be used to perform attenuation correction on the SPECT-MPI imaging data to generate corrected SPECT-MPI imaging data. The deep-learning model can be trained using corresponding pairs of non-corrected SPECT-MPI imaging data and traditional CT-AC imaging data. The deep-learning model can be a conditional generative adversarial neural network (cGAN).

Abstract: A method for performing real-time magnetic resonance (MR) imaging on a subject is disclosed. A prep pulse sequence is applied to the subject to obtain a high-quality special subspace, and a direct linear mapping from k-space training data to subspace coordinates. A live pulse sequence is then applied to the subject. During the live pulse sequence, real-time images are constructed using a fast matrix multiplication procedure on a single instance of the k-space training readout (e.g., a single k-space line or trajectory), which can be acquired at a high temporal rate.

Abstract: The present invention provides for methods of differentiating induced pluripotent stem cells into pancreatic progenitor cells, pancreatic ductal cells, pancreatic endocrine cells, pancreatic acinar cells, and pancreatic organoids. Cells created by these methods are also provided. Further provided are disease models and methods of drug screening.

Abstract: Systems and methods are disclosed for automatically performing motion correction in dynamic positron emission tomography scans, such as dynamic positron emission tomography myocardial perfusion imaging studies. An automated algorithm can be used. The algorithm can use simplex iterative optimization of a count-based cost-function customized to different dynamic phases for performing frame-by-frame motion correction.

Abstract: Described herein is the production neural progenitor cell lines (NPCs) derived from human induced pluripotent stem cells (iPSCs). These iPSC-derived NPCs engraft efficiently into the spinal cord of ALS animal models and provide neuroprotection to diseased motor neurons, similar to the fetal-derived cells used in clinical study. Clonal lines were generated with a single copy GDNF construct inserted in the AAVS1 safe landing site, including inducible expression of GDNF expression. These new iPSC-derived NPC lines are scalable to clinically relevant production volumes, uniformly produce GDNF, are safe, and represent a promising new combination therapy for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS).

Abstract: Production of beta-cells from stem cells from pluripotent stem cells have always been significantly lacking in at least one of the following properties: 1) functional properties related to insulin-production and glucose signaling response, 2) mature phenotype such as biochemical markers or cell structures, 3) efficiency in production of differentiated cells. Described herein is multistep differentiation protocol which substantially overcomes all of the existing limitations. Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) can be differentiated using an embryoid body (EB) formation step, followed by B maturation via endothelial cells (EC) co-culturing and incubation with a sequential series of bone morphogenic protein (BMP)-related growth factor cocktails. The resulting cells displayed functional properties, including insulin-production and glucose signaling response, and mature phenotype of C-peptide expression.

Abstract: Mechanical chopping has been successfully used to expand both fetal and iPSC-derived neural progenitor cells to scales suitable for early phase clinical trials. However, this method is time-consuming, labor-intensive, and challenging to implement at larger scales. Described herein are methods, apparatuses and systems for a novel in-line passaging technique that maintains the expansion rate and cellular identity of mechanical chopping but that is faster, scalable, and can be implemented in a fully sealed system.

Abstract: Provided herein are methods for treating pancreatic cancer using a combination of radiotherapy and an agent that inhibits binding of PD-L1 to PD1 (e.g., durvalumab).

Abstract: Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease modeling applications. The Inventors herein developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-d differentiated mEBs. The Inventors generated mammary-like organoids from 10-d mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation.

Abstract: The present invention describes method for reducing Delayed Graft Function (DGF) and Ischemia/Reperfusion Injury (IRI) by intra-renal infusion of a C1 esterase inhibitor.

Abstract: An endoscopic device for use in a patient's body in disclosed. The endoscopic device may include an outer sheath having a proximal end and a distal end, a suction tube inside the outer sheath, a handle coupled to the distal end of the outer sheath, and a cap on the proximal end of the outer sheath, positioned to seal the proximal end of the outer sheath, wherein the outer sheath comprises a sterile appliance, wherein the cap is structured to open in response to a force applied through the suction tube, and wherein the suction tube comprises an internal cavity.

Abstract: The disclosed technology relates to a system for delivering UV-A/B light with a catheter to treat infectious or inflammatory disorders in a patient. While UV light in the UV-C range has traditionally been used to treat skin disorders and for focused ablation of plaques in the arteries and other targeted internal uses, it has not been developed for broader infection, inflammation or neoplasia treatment inside the human body. Here, the inventor(s) developed a system for emission of therapeutic doses of UV light via a catheter, capsule, endoscope, tube or port that can be used to manage internal infections and inflammatory conditions inside a patient.

Abstract: The present invention teaches minimally invasive apparatuses and methods for stabilizing and/or guiding medical instruments used in a variety of medical procedures, including (a) introducing one or more substances into a subject's body, (b) removing one or more substances from a subject's body, (c) manipulating a region of a subject's body, or (d) combinations thereof. Among the many advantages of the inventive apparatuses are their simplicity and adaptability to attach to a variety of retractors.

Abstract: The present invention generally relates to sensitizer compounds and their use in combination with Tyrosine Kinase Inhibitors (TKIs) for sensitizing tumor, cancer or pre-cancerous cells to TKI treatment. In particular, the present invention relates to administration regimes that combine TKIs such as Gefitinib or Icotinib with TKI-sensitizing DZ1 esters and amides conjugated to statin or platin-based drugs, or to Artemisinin, including, without limitation: DZ1-Simvastatin amide, DZ1-Simvastatin ester, DZ1-Cisplatin ester, and DZ1-Cisplatin amide, DZ1-Artemisinin ester, and DZ1-Artemisinin amide. Furthermore, the present invention relates to improved TKI treatment of cancers by sensitizing tumor, cancer or pre-cancerous cells, in particular cancers that develop TKI resistance, including e.g. lung cancer and pancreatic cancer.

Abstract: Heart failure with preserved ejection fraction (HFpEF) is a disease condition characterized by heart failure (HF) signs and symptoms, but with normal or near normal left ventricular ejection fraction (LVEF) and is not responsive to standard therapy for treatment of HF. Described herein are compositions and methods related to use of cardiosphere derived cells (CDCs) and their exosomes to improve left ventricular structure, function and overall outcome. Administration of CDCs led to improved LV relaxation, lower LV end-diastolic pressure, decreased lung congestion and enhanced survival. Lower risk of arrhythmias in HFpEF was also observed following CDC administration. Improvement of diastolic dysfunction following administration of CDC-derived exosomes was observed, along with decreased mortality. In view of these salutary effects, CDCs and CDC-derived exosomes are beneficial in the treatment of HFpEF.