Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions including apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do not reduce the efficacy of the CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm including administration of a composition including apoptotic cells or an apoptotic cell supernatant.

The present invention provides a method of constituting a tissue construct in vitro using a tissue without depending on scaffold materials. A method of integrating a biological tissue with a vascular system in vitro, comprising coculturing a biological tissue with vascular cells and mesenchymal cells. A biological tissue which has been integrated with a vascular system by the above-described method. A method of preparing a tissue or an organ, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the biological tissue described above into a human or a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of preparing a non-human chimeric animal, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or organ in which vascular networks have been constructed. A method of evaluating a drug, comprising using at least one member selected from the group consisting of the biological tissue described above, the tissue or organ prepared by the method described above, and the non-human chimeric animal prepared by the method described above. A composition for regenerative medicine, comprising a biological tissue which has been integrated with a vascular system by the method described above.

The methods and compositions described herein surprisingly increase CRISPR/Cas-mediated gene editing in stem cells by transiently treating the cells with a stem cell viability enhancer prior to and/or after contacting the cells with one or more CRISPR/Cas9 components. Further, this treatment also surprisingly results in increased engraftment of the stem cells into the target tissue of a subject. The present disclosure also provides one or more modified CRISPR/Cas9 components which, when used in combination with the stem cell viability enhancer, further increases the frequency of gene editing in stem cells, increases stem cell viability, and increases stem cell engraftment.

The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

Provided are compositions and methods for producing modified non-human animals that produce heavy chain only antibodies (HCAbs), and modified non-human animals produced by the compositions and methods, and isolated HCAbs produced by the HCAbs.

A primatized rodent or swine, and methods of making and using the primatized rodent or swine, are provided.

A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.

Provided are non-human animals, including humanized bone marrow/liver/thymus (BLT) non-human animals, that include a recipient immunodeficient animal with human thymus tissue and human liver tissue, both implanted under a kidney capsule of the recipient immunodeficient animal, and transplanted hematopoietic stem cells derived from a human liver tissue. Such non-human animals have human thymus tissue and human liver tissue that are autologous with the hematopoietic stem cells derived from the human liver tissue. Methods of making such BLT non-human animals are also provided. Also disclosed herein are human immune system non-human animals and methods of making the same.

The invention relates to a new, spontaneous mouse lymphoma cell line displaying CD19, B220, MHC II, surface IgG2a/kappa chain and MAC-1, which is negative for CD5, animal models of B-cell lymphoma based on said cell line and methods for assessing lymphoma propagation and lymphoma expansion based on said cell line.