The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of two genes that weaken the function of the immune cell.

The engineered system disclosed herein takes extracted adult stem cells from individual mammal organs (such as adipose fat, bone marrow, or blood) and epigenetically rejuvenates the adult stem cells ex vivo back to a youthful fetal state using chemically defined small molecules. The rejuvenated multipotent stem cells are then exponentially expanded ex vivo in an automated bioreactor under novel conditions that maintain the youthful stem cell function while greatly reducing the risks of producing cancer stem cells. In another variation, this engineered system can also include improving the genetics of autologous adult stem cells using CRISPR base editing of genes affecting all-cause morbidity or mortality or genetic mutations. With or without gene editing, rejuvenated autologous multipotent stem cells are then reintroduced back into an organ or injected systemically into the circulation or bone marrow. The engineered system also includes small molecule treatment of the mammal around the time of stem cell injection to promote tissue regeneration and stem cell engraftment. The engineered system has the potential to promote overall health and longer life expectancy in humans, cats, dogs, and other mammals. The rejuvenated stem cell and small molecule systems offer the potential to treat a wide variety of diseases and disorders such as heart failure, kidney disease, Chronic Pulmonary Disease, frailty, various cancers, rare genetic diseases via CRISPR treated stem cells, and brain diseases such as Alzheimer's, Parkinson's, and vascular dementia. The engineered system treatment with rejuvenated stem cells also has the potential to reverse aging and reduce mortality in humans, dogs, cats, and horses.

Provided herein are endocrine progenitor cells and organoids derived from adult islets in vitro, as well as methods for making and using the same. The compositions are useful for treating or preventing diabetes, other diseases or disorders characterized by impaired islet function, and symptoms thereof.

The present invention relates to the field of cell therapy, and specifically relates to a method for producing a mesenchymal stem cell population, the mesenchymal stem cell population and a culture supernatant thereof produced by the method, and a pharmaceutical composition containing such cells or the culture supernatant thereof. The present invention further relates to use of the mesenchymal stem cell population and the culture supernatant thereof for preventing and treating diseases.

The present invention aims to provide a method for preparing an RPE cell, and an RPE cell prepared by the method, and a reagent for producing an RPE cell which is suitable for the method. The method of the present invention includes the following step: a step of introducing, as exogeneous factors, MITF (Microphthalmia-Associated Transcription Factor) gene or an expression product thereof, OTX2 (Orthodenticle homeobox 2) gene or an expression product thereof, LIN28 gene or an expression product thereof, and L-MYC gene or an expression product thereof into a mammalian somatic cell.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic endocrine cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

It is provided a method of producing high-quality engineered cartilage graft in a human of animal, such as nasal cartilage graft, comprising expanding chondrocytes and/or chondroprogenitors, e.g. autologous human nasoseptal chondrocytes (hNC,) from a donor patient by selecting expanded chondrocytes and/or chondroprogenitors by detecting the expression of at least one surfaceome protein gene or secretome protein gene, wherein the at least one surfaceome protein gene is ADGRG1, NPR3, SLC16A4, TSPAN13, FZD4 and SLC22A23 and the at least one secretome protein gene is ADGRG1, B3GNT7, COLGALT2, IGFBP3, STC2, SAA1, ANGPLT1, COL8A2, INHBB, ADAMTS9, ORM1, COL14A1, DCN, COL21A1, ENOX1, IL7, MXRA5 GAL, TFRC, SERPINA9, LIF, GDF6 and COL5A3.

The invention relates to improved methods for culturing an epithelial stem cell or an organoid comprising epithelial stem cells. The invention also relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

Provided are methods for expanding stem cells and/or lineage committed progenitor cells, such as hematopoietic stems cells and/or lineage committed progenitor cells, at least in part, by using compounds that antagonize AhR. The compounds are represented by formulae:

##STR00001## wherein the letters and symbols a, b, c, d, e, f, g, Z, R.sup.1b, R.sup.2a and R.sup.2b have the meanings provided in the specification. Also provided are compositions comprising stem cells and/or lineage committed progenitor cells expanded by methods disclosed herein and methods for the treatment of diseases treatable by same.

Human raphe nuclei organoids or spheroids (hRNS) are generated in vitro, which may be generated at least in part from human pluripotent stem (hPS) cells. Such spheroids model the human raphe nuclei and comprise specific sets of cells, e.g. serotonergic neurons, that are associated with the raphe nuclei of a human, and can be assembled with cortical spheroids (hCS) to generate functional human neuromodulatory circuits.