Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein.

Abstract: A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

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.

Abstract: A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the I NSM 1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (?24E1A) and the herpes simplex virus thymidine kinase gene. The I NSM1-promoter-driven viruses could replicate specifically in the I NSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas.

Abstract: Disease model pigs produced by nuclear transplantation, disease model pigs exhibiting stable phenotypes and production methods thereof are provided. Chimeric pigs for producing disease model pigs exhibiting stable phenotypes, genital glands thereof, and germ cells thereof are also provided. A method for producing a genetically modified disease model pig, includes: (a) transplanting a nucleus of a genetically modified cell into cytoplasm of an egg; (b) developing an obtained clonal embryo in a womb of a female pig to obtain an offspring; and mating the obtained offspring or having the offspring undergo sexual reproduction to further obtain the genetically modified offspring as a disease model pig.

Abstract: A 3-dimensional block type bone graft includes a plurality of first channels extending horizontally in forward and backward directions and arranged at a predetermined interval in left and right directions and upward and downward directions, a plurality of second channels extending horizontally in the left and right directions and arranged at a predetermined interval in the forward and backward directions and the upward and downward directions, and a plurality of third channels extending vertically in the upward and downward directions and arranged at a predetermined interval in the forward and backward directions and the left and right directions, wherein the first channels, the second channels, and the third channels intersect perpendicularly to each other to communicate with each other so that the first channels, the second channels, and the third channels are configured in a 3-dimensional shape.

Abstract: The present disclosure relates to the genetically modified non-human animals that express a human or chimeric (e.g., humanized) T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and methods of use thereof.

Abstract: Disclosed are a method for preparing induced pluripotent stem cells from endocardium-derived adult stem cells isolated from peripheral blood and a method for differentiating induced pluripotent stem cells into cardiovascular cells. The endocardium-derived adult stem cells are primary culture cells for preparing induced pluripotent stem cells, can be readily isolated and cultured only with a small amount of peripheral blood, have a high proliferation property so as to be storable without generic variation, and can rapidly ensure a cell number so as to be usable in cell therapy. The endocardium-derived adult stem cells have sternness, thereby having high preparation efficiency, and are derived from the endocardium so as to have the epigenetic memory of cardiovascular cells, thereby having an advantage of being able to be differentiated, after preparing induced pluripotent stem cells, into cardiovascular cells such as endothelial cells, smooth muscle cells and cardiomyocytes with a high efficiency.

Abstract: The present invention relates to a nutritional composition comprising at least one fucosylated oligosaccharide and at least one N-acetylated oligosaccharide in particular amounts, for use in preventing and/or treating infections and/or inflammations of the lower respiratory tract and/or of the ear in an infant or a young child.

Abstract: The disclosure provides vectors for treating cancers, method of producing such vectors and methods of use of the vectors.

Abstract: Disclosed herein are compositions and methods of fixing and staining rare cells. Further, disclosed herein are methods of identifying circulating tumor cells (CTC). In some embodiments, the method includes: imaging a cell sample to identify a cell of interest; determining a first pixel intensity of a stained nuclear area; determining a second pixel intensity of a background area; calculating a ploidy status of the cell of interest by subtracting the second pixel intensity from the first pixel intensity; and determining whether the cell of interest is a CTC based on the ploidy status. The method may be computer implemented, such that the method uses a machine learning algorithm to identify a feature; process the feature to extract a parameter of interest; analyze the parameter of interest; and when the parameter of interest is greater than or less than a predetermined threshold, classify the cell of interest as a CTC.

Abstract: The present invention is concerned with an automated method for obtaining at least one discrete colony from microorganisms or cells comprised in a solution. This method includes a step where acoustic liquid transfer is employed. The present invention further relates to the use of an acoustic liquid transfer device for obtaining at least one discrete colony from micro organisms or cells comprised in a solution. The present invention also relates to an automated method for determining the presence and/or quantity of microorganisms or cells potentially comprised in a solution and to the use of an acoustic liquid transfer device for determining the presence and/or quantity of microorganisms or cells potentially comprised in a solution.

Abstract: A dried vitrigel membrane is produced by a method including the following steps of (1) a step of keeping a hydrogel in the inside of a wall surface mold with a shape the same as the desired shape disposed on a substrate, and discharging a part of free water within the hydrogel from a gap between the substrate and the wall surface mold; (2) a step of removing the wall surface mold from the top of the substrate; (3) a step of drying the hydrogel to remove the residual free water, thereby fabricating a vitrified dried hydrogel; (4) a step of rehydrating the dried hydrogel to fabricate a vitrigel membrane; and (5) a step of redrying the vitrigel membrane to remove free water, thereby fabricating a vitrified dried vitrigel membrane.

Abstract: In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

Abstract: The present invention is directed to methods of inhibiting cancer cell growth or proliferation by contacting the cancer cell with an extracellular matrix (ECM) composition. Also provided are methods of delivering a chemotherapeutic agent to a cancer cell by contacting a cancer cell with an extracellular matrix composition containing a chemotherapeutic agent. Also provided are compositions containing ECM and a chemotherapeutic agent.

Abstract: Provided are a diluent and a sperm preservation method using the diluent. The diluent is useful in preservation of sperm with high fertility, and is capable of stably achieving quality control and improving quality of the sperm. Refrigerating or freezing sperm using the diluent for sperm, which includes an aqueous solution containing at least one oligosaccharide selected from the group consisting of a fructo-oligosaccharide, an isomalto-oligosaccharide, a gentio-oligosaccharide, and a galacto-oligosaccharide, can improve the quality of preserved sperm and provide sperm having high fertility, at a reduced cost.

Abstract: Disclosed herein is a method of producing acellular cartilage grafts. The method includes steps of, subjecting a cartilage matrix derived from an animal to alkaline, disinfection and decelluarization treatments. The thus produced cartilage graft is devoid of any cellular matters, while maintaining the porosity and integrity of collagen fibers therein, thus is suitable as a xenograft for host cells to grown thereon. Also disclosed herein is a method for treating osteochondral disease of a subject, in which the present acellular cartilage graft is applied to a lesion site of the subject.

Abstract: The invention relates to a method for producing a mesenchymal stem cell (MSC), the method comprising culturing a primitive mesoderm cell in a mesenchymal colony forming medium (M-CFM) comprising LiCl and FGF2, but excluding PDGF, under normoxic conditions for sufficient time for a mesenchymal colony to form, and culturing the mesenchymal colony adherently to produce the MSC, wherein the MSC has superior T-cell immunosuppressive properties relative to an MSC not produced in said M-CFM. The invention also relates to an MSC produced by the method, a population of MSCs produced by the method, a therapeutic composition comprising the MSC produced by the method, an M-CFM and an M-CFM in concentrated form, and method and uses of the MSC or population in treating a disease.

Abstract: Provided is a method for developing a secondary organ by using a non-human animal in which organ formation is inhibited, for the purpose of establishing a process for producing a functional cell such as a ? cell within the body of an animal such as a pig, the method including the step of raising a newborn or a fetus of the non-human animal in which organ formation is inhibited by complementing at least a part of the function of the organ whose formation is inhibited.