Abstract: The invention includes materials and methods to generate numerous small RNAs from one polynucleotide construct (synthetic gene) to facilitate RNA-guided multiplex genome editing, modification, inhibition of expression and other RNA-based technologies. The synthetic gene/polynucleotide construct encodes polycistronic RNA components separated by tRNAs, and preferably also includes regulatory components such as a promoter or terminator to form an expression cassette. Once transcribed in a cell, the transcript is processed by the cell to multiple RNA molecules by the endogenous tRNA processing system. The system can be sued for any RNA based gene manipulation method including RNA-mediated genome editing, artificial microRNA mediated gene silencing, small RNA mediated genetic manipulation, double-stranded RNA mediated gene silencing, antisense mechanisms and the like.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: Molecular signatures that function as very sensitive diagnostic biomarker for myocarditis, heart disease and disorders thereof, are identified.

Abstract: In one aspect, the present disclosure provides a method for identifying treatment targets relating to tumors. In another aspect, the present disclosure provides a method for identifying biomarkers and molecular features of normal and cancer cells.

Abstract: Disclosed are compositions, methods, and kits for modifying DNA within cells as well as compositions and methods for modifying gene expression in a cell. In particular, the invention generally relates to compositions, methods, and kits for DNA editing using single-stranded DNA. Compositions and methods for modifying gene expression using artificial microRNAs (amiRNA) are also contemplated.

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a TGF?R2 gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

Abstract: An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy useful for treatment of various hematopoietic disorders is provided. A method for expanding hematopoietic stem cells and/or hematopoietic progenitor cells, which comprises culturing hematopoietic stem cells and/or hematopoietic progenitor cells ex vivo in the presence of a compound represented by the formula (I) (wherein X, Y, X, Ar1, R1, R2, R3, R4, R5, R6 and R7 are defined in the description), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof.

Abstract: The present invention relates to methods and compositions concerning isolation of proliferating cells. In particular, the invention regards enrichment of stem cells in a mixture of stem cells and non-stem cells, wherein the non-stem cells may be differentiated cells. The invention exploits the non-adherent property of stem cells, as opposed to the adherent property of differentiating cells, by serially passaging the suspended cells in liquid media.

Abstract: A method of treating ischemia in a subject in need thereof is disclosed. The method comprising administering to the subject a therapeutically effective amount of adherent cells of a tissue selected from the group consisting of a placenta and an adipose tissue, thereby treating the ischemia in the subject. A method of treating a medical condition requiring connective tissue regeneration and/or repair is also disclosed.

Abstract: A method of treating chronic post-myocardial infarction including helical needle transendocardial delivery of autologous bone marrow (ABM) mononuclear cells around regions of hypo or akinesia in chronic post-myocardial infarction (MI) patients. The treatment is safe and improves ejection fraction (EF).

Abstract: A method of treating chronic post-myocardial infarction including helical needle transendocardial delivery of autologous bone marrow (ABM) mononuclear cells around regions of hypo or akinesia in chronic post-myocardial infarction (MI) patients. The treatment is safe and improves ejection fraction (EF).

Abstract: A method is provided for measuring inhibition of platelet reactivity in an individual treated with a drug-eluting stent (DES). First, a blood sample is obtained from an individual treated with a DES and a P2Y12 antagonist. The blood sample is then mixed with particles comprising an attached GPIIb/IIIa receptor ligand, adenosine diphosphate (ADP) and prostaglandin E1 (PGE1). The mixture is incubated under conditions suitable for agglutinating particles, and platelet-mediated agglutination is assessed in the mixture. The absence or reduction of agglutination indicates that the individual treated with a DES has reduced platelet reactivity. Also provided is a kit for measuring inhibition of platelet aggregation by a P2Y12 receptor antagonist that includes a GPIIb/IIIa receptor ligand immobilized on a particle, adenosine diphosphate (ADP), prostaglandin E1 (PGE1), an anticoagulant, and a buffer to maintain the anticoagulated blood in a condition suitable for platelet aggregation.

Abstract: The present invention provides novel stem cell compositions having significant therapeutic and practical advantages, as well as methods of preparing and using such compositions for the treatment and prevention of injury and disease in patients. The invention may be applied to stem cell populations isolated from a wide variety of animals, including humans, and tissues. In particular applications, the invention is used to prepare a stem cell composition from a collagen-based tissue, such as adipose tissue, isolated from a patient, and the stem cell composition is subsequently provided to a site of actual or potential injury in the patient. The invention further includes related kits comprising the stem cell compositions, which are remarkably stable and retain viability and efficacy during storage and shipment.

Abstract: The invention provides improved methods for cell therapy. In particular, the invention provides therapeutic compositions of enhanced hematopoietic stem and progenitor cells having improved engraftment and homing properties, and methods of making the therapeutic compositions. The invention further provides methods of improving the efficacy of hematopoietic stem and progenitor cell transplantation including transplanting the therapeutic composition to subjects in need of hematopoietic system reconstitution.

Abstract: This present application describes a therapeutic agent for treating acute or chronic graft-versus-host disease using clonal marrow stem cells (cMSCs) as active ingredient.

Abstract: A method is provided of determining whether an individual has reduced ability to form platelet thrombi due to inhibition of platelet activation initiation, signal transduction and/or GPIIb/IIIa blockade. A blood sample is obtained from the individual being assessed. The blood sample is mixed in combination with 1) an anticoagulant; 2) sufficient buffer to maintain the pH and salt concentration of the anticoagulated blood within a range suitable for platelet aggregation; 3) a platelet GPIIb/IIIa receptor ligand immobilized on a solid surface; 4) one or more agents to enhance a signal transduction pathway and 5) a receptor activator. The combination is incubated under conditions for agglutinating particles. Platelet-mediated agglutination is assessed in the agitated mixture. The absence of agglutination indicates that the individual has a reduced ability to form platelet thrombi.

Abstract: An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy useful for treatment of various disorders is provided. An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells is provided, containing a compound represented by the formula (I): (wherein X, Y, Z, Ar1 , R1, R2, R3, R4, R5, R6 and R7 are as defined in the description), a tautomer, amide, ester, or pharmaceutically acceptable salt of the compound or a solvate thereof, which can expand hematopoietic stem cells and/or hematopoietic progenitor cells.

Abstract: The present invention relates to a method of isolating hematopoietic stem cells from adipose tissue. The method yields a notably high number of CD34+, ALDHbr and/or ABCG2-expressing cells, comprising hematopoietic stem cells, permitting the use of the cells with no or minimal expansion.

Abstract: The present invention provides a method to derive hepatic stem cells from stem cells derived from non-liver tissue. In one embodiment of the invention, hepatic stem cells are derived from adipose stem cells. The invention also provides a method of enhancing hepatic cytokine production (e.g., HGF) from ASCs, which may be useful in the regeneration of liver tissue when transplanted in vivo. Tissue culture conditions, including media conditions, are provided.

Abstract: The invention relates to a process for producing organic acids, acid derivatives thereof and/or organic alcohols. In particular, the invention relates to a process for culturing a butyric acid-producing micro-organism in a culture vessel; transferring a portion of the butyric acid which is produced in the culture vessel to a separate compartment; and then reintroducing a portion of the acids from the second compartment in a controlled manner into the culture vessel. The invention also relates to a process for making butanol. The invention further relates to a process for culturing a butyrate-producing micro-organism in a first compartment of an electrochemical reactor, passing a direct current electric field across the electrochemical reactor and harvesting butyric acid or acid derivatives thereof in a second compartment of the reactor. The invention further relates to a process for producing butanol from the butyric acid.