A composition having tissue repair activity, which is capable of promoting reactions associated with tissue repair, contains at least one selected from the group consisting of a first component that is a protein having a monocyte chemotactic protein-1 (MCP-1) activity, a second component that is a protein having the extracellular domain activity of sialic acid-binding immunoglobulin-type lectin-9 (Siglec-9), and a third component that is at least one of chondroitin sulfate and chondroitin sulfate proteoglycan.

We report human cerebellar organoids which recapitulate the major milestones of cerebellar development including generating bona fide Purkinje cells, as well as methods of making and using these human cerebellar organoids such as uses in drug target identification and drug screening. In various embodiments, we report a human organoid model (human cerebellar organoids [hCerOs]) capable of developing the complex cellular diversity of the fetal cerebellum, including a human-specific rhombic lip progenitor population that have never been generated in vitro prior to our study. 2-month-old hCerOs form distinct cytoarchitectural features, including laminar organized layering, and create functional connections between inhibitory and excitatory neurons that display coordinated network activity. Long-term culture of hCerOs allows healthy survival and maturation of Purkinje cells that display molecular and electrophysiological hallmarks of their in vivo counterparts, addressing a long-standing challenge in the field.

The present disclosure relates to methods for performing assays for active migration and cytotoxicity of a therapeutic agent towards tumor cells, e.g., immune cell and/or drug homing, migration, and tumor cytotoxicity. The methods are performed in labware that provide opportunities for a therapeutic agent, such as an immune cell or a drug, to migrate toward tumor cells, including tumor cells growing in a 3D spheroid conformation. The methods allow for, among other uses, the investigation of the effects of a therapeutic agent, such as immune cells or a drug, on tumor cells, and enable the investigation of homing, tumor cytotoxicity, and tumor immune evasion in a single, easy-to-use, high throughput system for more in vivo-like testing.

The present invention relates to a method for preparing lymphoid progenitors. The inventors took advantage of their original and relevant Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) Syndrome (WS) model and the access to blood samples from five WS patients to investigate the impact of CXCR4 desensitization on BM and extra-medullary (i.e. splenic) hematopoiesis and hematopoietic stem and progenitor cells (HSPCs) recirculation. They developed, for the first time, an original in vitro system permitting to selectively expand HSPCs to obtain lymphoid progenitors by using an original cocktail of cytokines. In particular, the present invention relates to an in vitro method for preparing lymphoid progenitors by culturing HSPCs in an appropriate culture medium comprising an effective amount of a cocktail of cytokines consisting in SCF, IL-3, IL-6, IL-7, Flt-3, and CXCL12.

Methods of obtaining mononuclear blood cells are provided. Also provided are methods of using the obtained cells for treating diseases such as cancer, infectious disease, autoimmune disease, allergy, and graft rejection.

A method of obtaining mesenchymal stem cells is provided. The method comprising: (a) administering to a subject an effective amount of a CXCR4 antagonistic peptide as set forth in SEQ ID NO: 1 so as to mobilize the mesenchymal stem cells to peripheral blood of the subject; (b) collecting the mesenchymal stem cells from the peripheral blood; and subsequently or concomitantly (c) purifying the mesenchymal stem cells using a mesenchymal stem cell-specific phenotype.

A composition having tissue repair activity, which is capable of promoting reactions associated with tissue repair, contains at least one selected from the group consisting of a first component that is a protein having a monocyte chemotactic protein-1 (MCP-1) activity, a second component that is a protein having the extracellular domain activity of sialic acid-binding immunoglobulin-type lectin-9 (Siglec-9), and a third component that is at least one of chondroitin sulfate and chondroitin sulfate proteoglycan.

A method for producing mature chondrocytes suitable for transplantation includes a cartilage culture step for culturing a cartilage using a first culture medium to give mature chondrocytes, wherein the first culture medium contains hydrocortisone and FGF-2. The cartilage is an auricular cartilage. The culturing step includes a step of culturing the cells under an environment of 2% or more and 15% or less of carbonic acid gas and 1% or more and 10% or less of oxygen gas against air.

In one embodiment, provided herein are cells, e.g., T cells expressing receptors that that cause a cell expressing the receptors to home to specific anatomical regions, e.g., the B cell zone of lymph nodes, the gastrointestinal tract, or the skin. Also provided herein is use of such cells, e.g., T lymphocytes, to treat diseases such as cancer.

The present invention relates to the ex vivo differentiation of NK cells from CD34+ hematopoietic stem cells. Such NK cells and their progenitor cells can be used in therapies of a broad range of malignancies. In the present invention it is shown that IL-12 modulates ex vivo NK cell differentiation. Specific, we achieved significantly higher expression of KIR, CD16 and CD62L in the presence of IL-12 in the cell culture system. The induction of receptor expression by IL-12 occurred predominantly on an augmented population of CD33+NKG2A+ NK cells early during NK cell differentiation. These cells further show enhanced cytolytic activity against MHC class I positive AML targets. In line with the enhanced CD16 expression, IL-12 modulated ex vivo generated NK cells exhibit an improved antibody-dependent-cytotoxicity, using anti CD20 antibody on various B cell targets. Additional to the enhanced expression of CD62L, we show that this cell population consists of a specific chemokine receptor profile. By showing an increased capacity for adhesion to lymphendothelial cells and a specific chemokine receptor profile, we show that IL-12 provided the ex vivo generated NK cells with specific tissue-homing abilities.