Abstract: The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD3e (T-cell surface glycoprotein CD3 epsilon chain), and methods of use thereof.

Abstract: Provided is a method for preparing mesenchymal stem cell-conditioned medium, including isolating mesenchymal stem cells from a subject, maintaining the mesenchymal stem cells in a mesenchymal stem cell maintenance medium, collecting the mesenchymal stem cells at passages 2 to 5, culturing the mesenchymal stem cells in a medium supplemented with fetal bovine serum and mesenchymal stem cell culture adjuvant for hours to obtain a mesenchymal stem cell-conditioned medium, harvesting the medium and centrifuging followed by filtering. Also provided is a method for preventing or treating epithelial tissue disorder of eyes such as dry eye syndrome, including applying the medium to an eye of a subject. Further provided is a medical composition including the medium.

Abstract: Disclosed herein include circuits, compositions, nucleic acids, populations, systems, and methods enabling cells to sense, control, and/or respond to their own population size. In some embodiments, an orthogonal communication channel allows specific communication between engineered cells. Also described herein, in some embodiments, is an evolutionarily robust ‘paradoxical’ regulatory circuit architecture in which orthogonal signals both stimulate and inhibit net cell growth at different signal concentrations. In some embodiments, engineered cells autonomously reach designed densities and/or activate therapeutic or safety programs at specific density thresholds. Methods of treatment are also provided in some embodiments.

Abstract: The present invention provides a small hairpin nucleic acid molecule that is capable of stimulating interferon production. The nucleic acid molecule of the present invention has a double-stranded section of less than 19 base pairs and at least one blunt end. In certain embodiments, the molecule comprises a 5? triphosphate or a 5? diphosphate.

Abstract: A method for inducing conversion from non-hepatic stem cells or non-hepatic progenitor cells into hepatic stem cells or hepatic progenitor cells, which comprises introducing any of the following combinations into the non-hepatic stem cells or non-hepatic progenitor cells: (a) a combination of HNF1, HNF6 and FOXA; (b) a combination of HNF1 gene, HNF6 gene and FOXA gene; (c) a combination of HNF1, MYC and FOXA; or (d) a combination of HNF1 gene, MYC gene and FOXA gene.

Abstract: Human decidual placental mesenchymal stem cell having an increased expression level of decoy receptor 3 (DcR3), and a method for obtaining the human decidual placental mesenchymal stem cells having an increased expression level of DcR3 are provided, wherein human decidual placental mesenchymal stem cells are cultured in a culture dish containing a serum-free medium and the DcR3 expression of the human decidual placental mesenchymal stem cells are increased by stimulation of at least one inflammatory cytokine for 48 hours, and obtaining the human decidual placental mesenchymal stem cells having an increased expression level of DcR3, wherein the increased expression level of DcR3 is significantly higher than that of human decidual placental mesenchymal stem cells with the stimulation is higher than that of human decidual placental mesenchymal stem cells cultured without the stimulation of the at least one inflammatory cytokine.

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: The present invention relates to the field of stem cell biology, in particular the lineage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC) in addition to nonembryonic human induced pluripotent stem cells (hiPSC), somatic stem cells, stem cells from patients with a disease, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC into floor plate midbrain progenitor cells and then further into large populations of midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons using novel culture conditions.

Abstract: The present disclosure provides a kit and method for constructing a long-acting depression animal model. The present disclosure adopts Bacille Calmette-Guerin (BCG) (or Mycobacterium bovis (M bovis)) and low-dose pertussis toxin (PTX) for combined induction, which greatly reduces modeling cost. A mouse model constructed by the method of the present disclosure can clearly distinguish a time interval of pathological behaviors from a time interval of depression-like behaviors and has prominent face validity and predictive validity. The method of the present disclosure is simple and convenient and does not require a large number of tedious daily operations as the depression model construction by chronic unpredictable stress, chronic restraint stress, social defeat, mother-child separation, or the like. The mouse model of the present disclosure can provide a valuable long-term intervention window for research on antidepressant therapy.

Abstract: Provided is a method for inducing pluripotent stem cells to differentiate into somatic cells in a culture medium containing a heparin binding growth factor, the method comprising bringing cells into contact with a conjugate of a laminin E8 fragment and a growth factor binding domain-containing fragment of a heparan sulfate proteoglycan. According to the present invention, pluripotent stem cells can be induced to differentiate into any desired somatic cells in a highly efficient manner.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a genetically modified Th17 cell to express a CAR having an antigen binding domain, a transmembrane domain, and an ICOS intracellular signaling domain.

Abstract: Provided herein are methods of reducing or eliminating undifferentiated pluripotent stem cells, where the methods comprise contacting an effective amount of a compound to a heterogeneous cell population or sample comprising or suspected of comprising differentiated cell types and undifferentiated pluripotent stem cells, whereby the contacting selectively reduces or eliminates undifferentiated pluripotent stem cells from the cell population or sample. Also provided are methods for obtaining a population of stem cell-derived cell types substantially free of undifferentiated pluripotent stem cells as well as isolated populations of such of stem cell-derived cell types.

Abstract: A nucleic acid molecule is uniquely designed and encodes an entire CRISPRi or CRISPRa system, while being sized for packaging within a single adeno-associated virus (AAV) vector. Examples of the nucleic acid molecule include about 4600 to 4700 base pairs. Examples of the nucleic acid molecule can include a nucleotide encoding a Cas polypeptide; a nucleotide encoding a repressor or an activator domain attached to the nucleotide encoding the Cas polypeptide via a linker; a first promoter operably connected to the nucleotide encoding the repressor or activator domain or the nucleotide encoding the Cas polypeptide; a nucleotide encoding an alpha-helical connecting the nucleotide encoding the Cas polypeptide to a nuclear localization signal (NLS); and a second promoter operably connected to a guide RNA (gRNA).

Abstract: A method of preventing or reducing the occurrence and/or development of a hernia within a subject at risk of developing a hernia includes implanting a graft material in contact with an opening in an abdominal wall. The graft material promotes healing of the abdominal wall and includes placental or placental derived tissue.

Abstract: Non-human animals, expressing humanized CD3 proteins are provided. Non-human animals, e.g., rodents, genetically modified to comprise in their genome humanized CD3 proteins are also provided. Additionally, provided are methods and compositions of making such non-human animals, as well as methods of using said non-human animals.

Abstract: The purpose of the present invention is to provide a cell creation method that enables a reduction in cost and time, that is highly safe, and that has great potential for being industrially applied. Provided by the present invention is a method for inducing differentiation of pluripotent cells in vitro into cells having a same phenotype and function as information-presentation cells, the method comprising co-culturing pluripotent cells or a cellular fraction having said pluripotent cells concentrated therein, together with damaged cells or dead cells derived from information-presentation cells, or together with a portion of the damaged cells or dead cells derived from information-presentation cells.

Abstract: The invention provides a composition comprising an extraembryonic endodermal (XEN) call and/or an embryonic fibroblast (EF) cell. The invention also provides a method of establishing a XEN cell line or a primary embryonic fibroblast (EF) cell line in vitro, the method comprising culturing a zygote or parthenote from a mammal for a time sufficient to produce one or more blastocysts; and culturing the one or more blastocysts on feeder cells in culture medium for a time sufficient to produce one or a plurality of XEN cells and/or one or a plurality of EF cells.

Abstract: Provided is a genetically modified non-human animal, in which at least one copy of the endogenous nucleotide sequence encoding Protein C in the genome of said the non-human animal has been replaced by a nucleotide sequence encoding human Protein C or a functional fragment or variant thereof. Also provided are vectors, cells, and methods for the production of such non-human animals. Further provided are methods of testing agents for their ability to alter to the level and/or functional activity of human protein C, for example, to test their potential therapeutic efficacy.

Abstract: The present invention provides a disease model animal for tauopathies which reproduces the expression pattern of tau protein isoforms of adult human brain, that is, approximately equal amounts of 3R type tau and 4R type tau being expressed in the adult brain. The method for producing the disease model animal for tauopathies of the present invention comprises the steps of: preparing a tau seeds; and injecting the tau seeds in the brain of an animal carrying a mutation in the tau gene which fails to express the tenth exon. The animal carrying a mutation in the tau gene which fails to express the tenth exon may be produced by using any of the genome editing, gene targeting or base editing technologies.

Abstract: The present invention relates to RNA therapy and, in particular, decreasing immunogenicity of RNA. Specifically, the present invention provides methods for decreasing immunogenicity of RNA, said methods comprising modifying the nucleotide sequence of the RNA by reducing the uridine (U) content, wherein said reduction of the U content comprises an elimination of U nucleosides from the nucleotide sequence of the RNA and/or a substitution of U nucleosides by nucleosides other than U in the nucleotide sequence of the RNA. Using RNA having decreased immunogenicity allows administration of RNA as a drug to a subject, e.g. in order to obtain expression of a pharmaceutically active peptide or protein, without eliciting an immune response which would interfere with therapeutic effectiveness of the RNA or induce adverse effects in the subject.