The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

Disclosed is a humanized 4-1BB monoclonal antibody, an antigen-binding fragment thereof, a pharmaceutical composition and a medical use thereof. The monoclonal antibody comprises CDR1 with the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 4, CDR2 with the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 5, CDR3 with the amino acid sequence shown in SEQ ID NO: 3, CDR1′ with the amino acid sequence shown in SEQ ID NO: 6, CDR2′ with the amino acid sequence shown in SEQ ID NO: 7, CDR3′ with the amino acid sequence shown in SEQ ID NO: 8. The monoclonal antibody binds to human 4-1BB with high affinity and specificity, leads to a significant increase in T cell proliferation and TNF-γ production, and enhances and stimulates human 4-1BB-mediated immune response.

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 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.

A bio-related substance bonded to a branched and degradable polyethylene glycol derivative that is degraded in the cells represented by the following formula (A):

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wherein each symbol is as defined in the present specification, is provided by the present invention.

The present invention relates to a composition for preventing or treating diabetes mellitus using a 4-component mixture of putrescine, glucosamine, nicotinamide, and a STAT3 inhibitor. It has been confirmed that blood glucose is stably regulated when a compound of the 4-component mixture according to the present invention is injected into the caudal vein of a diabetes mellitus-induced mouse. The compound can be practically and usefully used as a therapeutic agent for diabetes mellitus patients and patients exposed to diabetes mellitus risk.

This disclosure relates to immunogenic peptides that are specific to B-cell maturation antigen (BCMA) and Transmembrane activator and CAML interactor (TACI), and methods of use thereof.

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.