The technology described herein is directed to stromal-free methods of NK cell differentiation. Also described herein are cells differentiated using stromal-free methods and compositions comprising such cells. In some embodiments, the cells can be genetically modified. In some embodiments, the cells or compositions comprising said cells can be administered to a patient to treat cancer or as a cellular replacement therapy to treat a condition.

A method for inducing conversion from non-hepatic stem cells or non-hepatic progenitor cells into hepatic stem cells or hepatic progenitor cells, which comprises introducing any of the following combinations into the non-hepatic stem cells or non-hepatic progenitor cells: (a) a combination of HNF1, HNF6 and FOXA; (b) a combination of HNF1 gene, HNF6 gene and FOXA gene; (c) a combination of HNF1, MYC and FOXA; or (d) a combination of HNF1 gene, MYC gene and FOXA gene.

The present invention provides for methods, compositions, and kits for producing an induced pluripotent stem cell from a non-pluripotent mammalian cell using a 3-phosphoinositide-dependent kinase-1 (PDK1) activator or a compound that promotes glycolytic metabolism as well as other small molecules.

Methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation.

Methods for accelerated cell lineage conversion and the treatment of patients with the lineage converted cells are provided. The methods include the steps of transfecting a cell with a composition that includes at least one synthetic mRNA encoding a chimeric protein that corresponds to an engineered fusion of a transcription factor and an heterologous peptide sequence derived from the C-terminal TAD of Gal4. The TAD domain enhances the epigenetic remodeling activity of the chimeric protein increasing the speed of lineage conversion. The converted cells may be used for research or administered to a human or animal patient as a therapy. In one preferred embodiment, the reprogramming of a somatic cell to pluripotency is accelerated by using a cocktail of mRNAs expressing a combination of wild-type or engineered reprogramming factors where Oct4 and/or Sox2 and/or Nanog are expressed as Gal4 TAD chimeras.

Described herein is a method for producing blood progenitor (hematopoietic progenitor cells) and T cell progenitor cells and to cells produced or obtainable by the process and the use of said cells, the method including: (a) optionally subjecting pluripotent stem cells under conditions that direct the cells to become mesoderm and subsequently hemogenic endothelial cells; and (b) directing hemogenic endothelial cells to differentiate into blood progenitor cells, preferably defined blood progenitor cells) using a media formulation designed to promote endothelial to hematopoietic transition (EHT) while being cultured on a surface functionalised with ligands designed to activate the Notch signaling pathway. In some aspects the ligands are Notch ligands, such as DLL4 and integrin ligands, such as integrin ?4?1 ligand or VCAM1.

The present invention provides for methods, compositions, and kits for producing an induced pluripotent stem cell from a non-pluripotent mammalian cell using a 3-phosphoinositide-dependent kinase-1 (PDK1) activator or a compound that promotes glycolytic metabolism as well as other small molecules.

Provided herein are methods and systems for bio-printing of three-dimensional organs and organoids. Also provided herein are bio-printed three-dimensional organs and organoids for use in the generation and/or the assessment of immunological products and/or immune responses. Also provided herein are methods and system for bio-printing three-dimensional matrices.

This present disclosure provides methods and pharmaceutical compositions for cell reprogramming and a pharmaceutical composition comprising the reprogrammed cells. In certain embodiments, the method of reprogramming a cell comprises reducing the expression of at least one barrier gene selected from the group consisting of ATF7IP, JUNB, ZNF207, Sp7, FOXA1, HEXIM2, SMARCA5, SOX15, CHST2 or NCEH1, or if the barrier gene is ATF7IP or SOX15, then the expression of a second barrier gene is also reduced. In another embodiment, the reprogramming method comprises reducing the expression of at least two barrier genes selected from the group consisting of ATF7IP, JUNB, ZNF207 and Sp7.

The invention is directed to generation of hematopoietic multi-lineage progenitors (HMLPs) from endothelial cells (ECs) by effecting forced expression of certain transcription factors in the ECs and culturing the ECs in serum free media in the presence of endothelial feeder cells. The HMLPs generated in accordance with this invention can produce erythroid, lymphoid, myeloid, and megakaryocyte cells. These generated HMLPs can be used in therapeutic treatment of disorders including hematopoietic conditions.