In some aspects, disclosed herein are methods and compositions for treatment or prevention of CNS disorders (e.g., stroke) using fibroblasts or derivatives thereof. Disclosed herein are fibroblasts and derivatives thereof capable of inducing neuroregeneration and/or reducing neuroinflammation in a subject. Aspects comprise methods and compositions for stimulating neural progenitor cell proliferation. In some cases, methods comprise providing fibroblasts and stem cells (e.g., hematopoietic stem cells) to an individual to treat or prevent a stroke. Embodiments are directed to exosomes or other microvesicles (e.g., apoptotic bodies) derived from fibroblasts for use in treating or preventing stroke in an individual. In some aspects, disclosed are means, methods, and compositions of matter useful for treatment of cerebral hemorrhage through administration of fibroblasts, modification of fibroblasts, and/or derivatives of fibroblasts such as exosomes, microvesicles, and/or apoptotic bodies. In one embodiment, fibroblasts, modified fibroblasts, and/or derivatives thereof are administered for induction of neuroprotective properties and/or stimulation of neuroregeneration.

In some aspects, disclosed herein are methods and compositions for treatment of sclerosing cholangitis using fibroblasts or derivatives thereof. The disclosed compositions include fibroblasts, engineered fibroblasts, exosomes obtained from fibroblasts, and conditioned media derived from fibroblasts. Methods of the present disclosure include providing fibroblasts to a subject to treat sclerosing cholangitis in the subject. Fibroblasts of the disclosure include fibroblasts capable of reducing inflammation in a subject. In certain aspects, fibroblasts are cultured with activating agents prior to therapeutic administration.

In some aspects, disclosed herein are methods and compositions for treatment of sclerosing cholangitis using fibroblasts or derivatives thereof. The disclosed compositions include fibroblasts, engineered fibroblasts, exosomes obtained from fibroblasts, and conditioned media derived from fibroblasts. Methods of the present disclosure include providing fibroblasts to a subject to treat sclerosing cholangitis in the subject. Fibroblasts of the disclosure include fibroblasts capable of reducing inflammation in a subject. In certain aspects, fibroblasts are cultured with activating agents prior to therapeutic administration.

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.

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.

Methods of increasing progenitor cell production are described. In particular, an effective amount of a thrombopoietin (TPO) mimetic is used to increase production of at least one cell selected from a stem cell, a progenitor cell or an endothelial cell in the bone marrow of non-irradiated subjects.

The disclosure relates to methods for detecting PNH Type II cell populations in biological samples as well as methods for determining whether a patient is at an increased risk for developing thrombocytopenia or thrombosis based on the percentage of PNH Type II cells in the patient's blood. The disclosure also features reagents and conjugates for use in the methods.

The present invention relates to a pharmaceutical composition for treating aplastic anemia, which comprises Romiplostim as an active ingredient, wherein the pharmaceutical composition is administered subcutaneously once a week, wherein Romiplostim is administered at 10 μg/kg/week for 4 weeks from the start of administration, administered at more than 10 μg/kg/week and at a maximum of 20 μg/kg/week after week 5.

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 mg/mL to 20 mg/mL).