Spheroid microtissues that can mimic native tissue-like structure and function, spheroid production methods that are high-throughput, suitable for efficient production, maintainable over long-term culture, and/or offer repeatable control over size distribution. Spheroids that have blood vessels, including spheroids with functional, blood-perfused vascular networks upon injection in vivo. Dissolvable hydrogel microwell arrays for high throughput parallel formation of spheroids in a single pipetting step and easy retrieval for downstream applications. A method to produce prevascularized microtissues in sufficient numbers to form a macrotissue in vivo for therapeutic purposes. This method is based on sacrificial release of dissolvable microwell templates, a novel and scalable strategy which enables gentle harvesting of microtissues with control over size and composition. The method forms microtissues containing endothelial cells and mesenchymal stem cells, which are co-cultured under dynamic conditions and self-organize into blood-vessel units.

The present invention in general relates to a method of differentiating human hematopoietic stem cells (HSC) into mature natural killer (NK) cells; wherein said method is in particular characterized in that mature NK cells are obtainable very early during the differentiation method, and that these NK cells display increased CD16 expression and antibody-dependent cellular cytotoxicity (ADCC) (FIG. 11). The method of the invention specifically encompasses transfecting and/or transducing HSCs with at least one transcription factor selected from T-Box expressed in T cells (T-BET) and Eomesodermin (EOMES); or a combination thereof.

Provided herein are isolated exosomes from mesenchymal stem cells (MSC). Such isolated exosomes are substantially CT free of contaminants and are therapeutically active in treating various diseases (e.g., lung diseases such as BPD). The isolated MSC exosomes are identified by one or more protein markers described herein. Methods of purifying such MSC exosomes are also provided.

Various embodiments of the invention provide methods of treating diabetes and other glucose regulation disorders. In one embodiment, the method comprises removing L-cells from a donor, obtaining stem cells from a patient, and culturing the L-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived L-cells (SCDLC). An amount of the SCDLC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food. In another embodiment, the method comprises removing K-cells from a donor, obtaining stem cells from a patient, and culturing the K-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived K-cells (SCDKC). An amount of the SCDKC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food.

Various embodiments of the invention provide methods of treating diabetes and other glucose regulation disorders. In one embodiment, the method comprises removing L-cells from a donor, obtaining stem cells from a patient, and culturing the L-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived L-cells (SCDLC). An amount of the SCDLC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food. In another embodiment, the method comprises removing K-cells from a donor, obtaining stem cells from a patient, and culturing the K-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived K-cells (SCDKC). An amount of the SCDKC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food.

The present disclosure provides a method for producing erythroid cells and/or erythrocytes comprising culturing hematopoietic stem cells (HSCs) or erythroid cells with a population of immortalized mesenchymal stem cells (MSCs) or conditioned medium obtained from the immortalized MSCs, wherein the immortalized MSCs are genetically engineered with a survival gene. Also provided is a method of making a blood product for use in transfusions and a method for increasing hemoglobin synthesis.

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES.sup.+ NK cells, T-BET.sup.+ ILC1, GATA-3.sup.+ ILC2 and for IL-22.sup.+ but not for IL-17A.sup.+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

The current invention concerns a composition for treating trauma in a subject, where the composition includes isolated mesenchymal stem cells (MSCs), wherein the MSCs are tenogenic-induced and/or chondrogenic-induced, and where the trauma is tendon trauma, traumas of the ligaments, or trauma of cartilage.

Disclosed are compositions of matter, protocols and procedures useful for preventing/treatment ovarian failure. In one embodiment cytokines promoting anti-inflammatory/regenerative activity are administered systemically, or locally in order to preventing ovarian degeneration/fibrosis. In one embodiment low dose interleukin-2 is administered either alone or with adjuvant cytokines to induce an increase in FoxP3 expressing CD4 cells. In some embodiments in vivo generation of FoxP3 expressing CD4 cells is associated with stimulation of intra-ovarian angiogenesis and prevention of fibrosis.

The present application provides methods and processes for making and using a fibronectin composition, as well as methods for treating ocular conditions and/or disorders with the cellular fibronectin composition described herein.