A composition inhibiting MEIS proteins. The MEIS proteins are effective in proliferation of hematopoietic stem cells. A formulation capable of easily passing through the cell membrane and perform its activity in the cell, and can inhibit MEIS activity in a dose dependent manner. The combination includes isolated cells, medium, growth factors and MEISi inhibitor. The isolated cells are isolated from mouse bone marrow, human bone marrow and human umbilical cord blood. The medium has a pH value of 7.2 and contains bovine serum albumin, recombinant insulin, transferrin, 2-mercaptoethanol and IMDM medium. The growth factors are hematopoietic stem cell factor SCF, fetus liver tyrosine kinase-3 ligand Flt3L, and thrombopoietin. A chemical formula of the MEISi-1 is 4-[2-(benzylamino)-2-oxoethoxy]-N-(2,3-dimethylphenyl) benzamide. A chemical formula of MEISi-2 is 4-hydroxy-N-[(Z)-(2-oxonaphthalen-1-ylidene)methyl] benzohydrazide.

Disclosed are compounds for use in modulating a mobilization of hematopoietic stem and progenitor cells (HSPCs) or hematopoietic stem cells (HSCs) from the bone marrow to the peripheral blood in a subject; wherein the compound inhibits the activity of cytochrome P450 family 7 subfamily B member 1 (CYP7B1 inhibitor).

A method for treating a defect site in a living bone of an animal by applying an exogenous compound having thrombopoietic activity to the defect site in an amount effective to induce thrombopoiesis. The exogenous compound activates a thrombopoietin receptor, leading to accelerated bone formation at the defect site. Also provided is a method for repairing a segmental bone defect in an animal bone by inserting into the segmental bone defect a biodegradable bone repair scaffold that contains a compound having thrombopoietic activity. The compound activates a thrombopoietin receptor and accelerates bone formation such that bridging occurs at the segmental bone defect.

This invention is in the area of improved compounds and methods for transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from the damage associated with ionizing radiation (IR) exposure using selective radioprotectants.

This invention is in the area of improved compounds and methods for transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from the damage associated with ionizing radiation (IR) exposure using selective radioprotectants.

The subject invention pertains to novel methods of treatment for subjects suffering from anemia, particularly as a result of erythropoiesis-stimulating agents (ESAs) resistant anemia. The methods comprise administering at least two compositions to a subject, in which the compositions can comprise a first composition comprising an ESA and a second composition comprising a thrombopoietin receptor agonist (TPO-RA). The combination of ESA with TPO-RA can stimulate the expansion of hematopoietic stem cells.

TPO was used to promote the growth of bone in both rats and in mice. Gaps in both mouse and in rat bones were treated with a scaffold sized to fit the gap. Scaffolds that included TPO promoted better outcomes than scaffolds that included BMP-2 or scaffolds that did not include either TPO or BMP-2. These data indicate that compounds that exhibit thrombopoietic activity such a recombinant TPO can be used to promote bone growth and healing in mammals.

This invention concerns a process for making a lyophilized pharmaceutical formulation of a therapeutic protein, which comprises (a) providing a formulation of a bulk amount of the therapeutic protein, (b) measuring the concentration of the therapeutic protein in said bulk formulation, (c) adjusting the fill weight of the protein in said bulk formulation to achieve a fixed dose of the protein, and (d) lyophilizing the protein fill weight-adjusted formulation to achieve a final formulation in a container, wherein the product concentration post reconstitution with a fixed volume is within a predetermined acceptance range. The process is particularly suitable for formulations with low protein concentrations (e.g., 0.05 to 20 mg/mL).

Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some embodiments, the NK cells or T cells express a thrombopoietin receptor or an erythropoietin receptor. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.

Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some embodiments, the NK cells or T cells express a thrombopoietin receptor or an erythropoietin receptor. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.