Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

The present disclosure provides, at least in part, methods and compositions for in vivo fusosome delivery. In some embodiments, the fusosome comprises a combination of elements that promote specificity for target cells, e.g., one or more of a fusogen, a positive target cell-specific regulatory element, and a non-target cell-specific regulatory element. In some embodiments, the fusosome comprises one or more modifications that decrease an immune response against the fusosome.

A vascular adhesion protein-1 (VAP-1) inhibitor can be used as a regulator of reactive oxygen species (ROS) concentration in ex vivo culturing of hematopoietic stem cells, which enables a method of producing an expanded population of hematopoietic5 stem cells ex vivo. Further, a VAP-1 inhibitor can be used in the treatment of bone marrow suppression or bone barrow failure in an individual.

In the various aspects and embodiments, this disclosure provides genetic, pharmacological, and mechanical stimuli for transitioning endothelial cells to hemogenic endothelial (HE) cells, and for transitioning HE cells to HSCs, including HSCs that comprise a significant level of LT-HSCs. The disclosure further provides methods for expanding HSCs using the genetic, pharmacological, and mechanical stimuli.

Compositions of purified biologically active Wnt proteins are provided. Wnt proteins are found to be hydrophobic and post-translationally modified by addition of a lipid moiety at a conserved cysteine residue. Methods for isolation of Wnt utilize detergents that maintain the solubility of the modified protein.

The present invention relates to methods of generating and expanding hitman embryonic stem cell derived mesenchymal-like stem/stromal cells. These hES-MSCs are characterized at least in part by the low level of expression of IL-6. These cells are useful for the prevention and treatment of T cell related autoimmune disease, especially multiple sclerosis, as well as for delivering agents across the blood-brain barrier and the blood-spinal cord barrier. Also provided is a method of selecting clinical grade hES-MSC and a method of modifying MSC to produced a MSC with specific biomarker profile. The modified MSC are useful for treatment of various diseases.

Described herein are methods and related compositions for inducing differentiation of human pluripotent stem cells (hPSCs) into hemogenic endothelium with pan-myeloid potential or restricted potential, by forced expression in the hPSCs of a combination of transcription factors as described herein.

The present invention is directed to compositions and methods to increase the expression of PD-L1 and/or IDO-1 in a population of cells, the modulated cells expressing increased PD-L1 and/or IDO-1, and methods related to the immunosuppressive effects obtained by cells expressing increased PD-L1 and/or IDO-1.

The present disclosure relates to populations of small pluripotent stem cells derived from peripheral blood, such as human peripheral blood. In some aspects, these small pluripotent stem cells are smaller than known stem cells and express a range of embryonic, hematopoietic, or mesenchymal stem cell markers. Also disclosed herein are methods of isolation and cryopreservation of these populations of small pluripotent stem cells. These small pluripotent stem cells may be differentiated in a wide range of cell types, which can be used in various applications such as the study of cell activity or for treatment of diseases and personalized medicine.

The present disclosure relates to, at least, a vacuum-assisted method for infiltrating cadaver bone with a cryoprotectant and a method for rapidly warming the cryopreserved cadaver bone for bone marrow processing.