A system and method for gene editing by using an engineered cell are provided. The system includes the engineered cell embedded with a synthetic protein receptor and a target cell. The engineered cell contains a CRISPR/CasRx system and a sgRNA gene sequence. The synthetic protein receptor includes an extracellular target cell recognition domain, a native Notch core domain, an intramembranous hydrolyzable polypeptide and effectors. The extracellular target cell recognition domain can recognize antigen molecules on the target cell surface; and the effectors act as transcription factors for CasRx enzyme and sgRNAs. CasRx and gRNA are expressed in the engineered cell for gene editing to edit mRNA of the target cell. In this way, the application range of the engineered cell is expanded, the pertinence and specificity of gene editing are improved, the off-target effect is reduced, the collective non-specific reaction is reduced, and the safety of gene editing is improved.

The disclosure generally relates to methods and compositions for preparing a neural tissue construct. In particular, provided herein are methods for generating a neural tissue construct using glutamatergic cortical progenitor cells; GABAergic interneuron progenitor cells; and bio-ink.

A therapeutic effect of Nurr1 and Foxa2 in inflammatory neurologic disorders by M1-to-M2 polarization of glial cells is provided. Specifically, a method of converting glial cells from an M1 phenotype to an M2 phenotype, wherein Nurr1 and Foxa2 are introduced into the glial cells to be overexpressed in the glial cells and a method of preventing or treating an inflammatory neurologic disorder, which includes glial cells into which Nurr1 and Foxa2 are introduced, or a viral vector loaded with Nurr1 and Foxa2, are provided.

The present disclosure provides multicellular culture models for the study of neuroinflammation, such as to identify novel targets, biomarkers, and therapeutic agents for the diagnosis, prognosis, and treatment of neurodegenerative diseases. Further provided herein are assays for studying neuroinflammation using the present cell culture models.

The present invention relates to methods of treating or ameliorating certain neurodegenerative disorders (namely, dysmyelinating and demyelinating disorders) in patients in need of such treatment or amelioration. The invention provides methods of treating or ameliorating a patient in need of such treatment and includes the administration to the patient of: (a) thyroid hormones or thyroid hormone analogues; (b) cell replacement therapies involving the use of homogenous Oligodendrocyte Precursor Cells derived from embryonic stem cells that have been treated with thyroid hormones or thyroid hormone analogues; (c) gene therapy to correct mutated genes in vivo; or (d) a combination of two or more of (a), (b) and (c). The invention also provides compositions and formulations of thyroid hormones and thyroid hormone analogues for use in treating or ameliorating such disorders.

The present invention relates to methods for making in vitro retinal cultures, tissue, or retinal organoids, from pluripotent cells as well as the improved synthetic retinal tissue and retinal organoids themselves. It also relates to retinal organoids that replicate in vitro many characteristics of the retina (e.g., human or mammalian), and methods of using this retinal organoid to study disease and to identify therapeutic agents for the treatment of retinal diseases and disorders.

The present disclosure relates to a method for obtaining human brain-like endothelial cells by contacting a population of cells isolated from stem cells with a differentiation medium to obtain endothelial cells and co-culturing said endothelial cells with pericytes, with cells of the neurovascular unit or with a pericytes conditioned medium, to obtain brain-like endothelial cells. The present disclosure also relates to the use of the brain-like endothelial cells as an in vitro model of human blood-brain barrier and a kit for measuring blood-brain barrier permeability of a substance, comprising in vitro human endothelial cells.

The invention provides a cell-containing vessel comprising a plurality of neural cell-containing spheroids for which the variation calculated using the calculation method described below is less than 20%, wherein the neural cell-containing spheroids contain a plurality of types of cells including neural cells,

(Calculation Method)

Calcium transient assays are conducted for each of a plurality of neural cell-containing spheroids, a number of spontaneous oscillations in a 10-minute period is measured, an average and standard deviation for the number of spontaneous oscillations are calculated, and a variation is calculated using formula (1) below:

Variation (%)=standard deviation for number of spontaneous oscillations/average number of spontaneous oscillations×100  (1).

A method of producing a cell-containing container is provided, including a process in which pluripotent stem cells that have been induced to differentiate into neurons, and astrocytes are mixed and seeded in a cell culture container in which an electrode array is arranged on a culture surface, and a process in which the cell culture container is incubated, and as a result, the pluripotent stem cells and the astrocytes adhere to the culture surface, and the pluripotent stem cells differentiate into neurons.

A method for obtaining a composition for tissue regeneration, providing M2-macrophages, co-culturing the M2-macrophages with tissue-specific cells in serum free medium; and collecting the supernatant of the co-culture. The compositions obtained by this method are suitable in medicine regenerative treatments, able to regenerate injured tissue. These products are sterile cell-free physiological aqueous solutions that show specific tissue concentration patterns to provide optimal tissue-specific regenerative effects. The compositions may be stored for long periods cryopreserved or lyophilized until its use, avoiding any subsequent blood extraction from the cell-donor, the stored growth factors and/or cytokines biologically active after long-term storage. Moreover, the compositions may be potentially applied in both autologous and allogenic treatments.