Abstract: In one aspect, anabolic agent fusion proteins and compositions comprising anabolic agent fusion proteins are provided. In some embodiments, the anabolic agent fusion protein comprises a platelet derived growth factor (PDGF) or a fibroblast growth factor (FGF) and an Asp-Ser-Ser tripeptide (DSS) repeat sequence. In another aspect, methods of promoting bone growth and methods of treating a fracture using anabolic agent fusion proteins and compositions comprising anabolic agent fusion proteins are provided.

Abstract: A vector for generating induced pluripotent stem cells from human target cells comprising a) a vector backbone, b) exactly two, three or four transcription and reprogramming factor genes, each gene separated by a 2a self-cleavage peptide sequence, c) a spleen focus-forming virus promoter, and d) a post-transcriptional regulatory element Wpre, with or without an anti-apoptotic factor gene. A method for generating integration-free induced pluripotent stem cells, the method comprising: a) providing target cells, b) providing one or more than one vector according to the present invention, c) transducing or transfecting the target cells with the one or more than one vector, and d) culturing the transduced or transfected cells in a cell culture, thereby generating integration-free induced pluripotent stem cells.

Abstract: Methods are disclosed herein for increasing bone mass and strength or bone fracture healing in a subject. The methods include administering to the subject a therapeutically effective amount of multipotent stem cells, wherein each multipotent stem cell is transformed with a recombinant nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid encoding platelet derived growth factor (PDGF) B, and wherein the multipotent stem cells express a sufficient amount of PDGFB to increase bone mass and strength or bone fracture healing. A lentiviral vector also is disclosed that includes a phosphoglycerate kinase-1 (PGK) promoter operably linked to a nucleic acid encoding PDGFB.

Abstract: A vector for generating induced pluripotent stem cells from human target cells comprising a) a vector backbone, b) exactly two, three or four transcription and reprogramming factor genes, each gene separated by a 2a self-cleavage peptide sequence, c) a spleen focus-forming virus promoter, and d) a post-transcriptional regulatory element Wpre, with or without an anti-apoptotic factor gene. A method for generating integration-free induced pluripotent stem cells, the method comprising: a) providing target cells, b) providing one or more than one vector according to the present invention, c) transducing or transfecting the target cells with the one or more than one vector, and d) culturing the transduced or transfected cells in a cell culture, thereby generating integration-free induced pluripotent stem cells.

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Abstract: Methods are disclosed herein for increasing bone mass and strength or bone fracture healing in a subject. The methods include administering to the subject a therapeutically effective amount of multipotent stem cells, wherein each multipotent stem cell is transformed with a recombinant nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid encoding platelet derived growth factor (PDGF) B, and wherein the multipotent stem cells express a sufficient amount of PDGFB to increase bone mass and strength or bone fracture healing. A lentiviral vector also is disclosed that includes a phosphoglycerate kinase-1 (PGK) promoter operably linked to a nucleic acid encoding PDGFB.

Abstract: A method for treating a patient with an episode of sepsis. A method for categorizing the severity of an episode of sepsis in a patient.

Abstract: Vectors, such as retroviral vectors and transposon-based nonviral vectors, are disclosed herein that can be used to target transgene expression to the proliferating periosteal cells and cells in the marrow space after bone fracture. In one embodiment, these vectors include a human Cox-2 gene that is modified to improve mRNA stability and protein translation by truncating the 3? untranslated region (UTR). In addition, in some embodiments, the native translation signal is replaced with an optimized Kozak sequence. These vectors can be used alone or with vectors expressing BMP2/4, FGF-2, or LMP-1 gene to repair bone fractures and increase prostaglandin secretion. Methods for identifying agents that accelerate bone repair are also disclosed.

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: A vector for generating induced pluripotent stem cells from human target cells comprising a) a vector backbone, b) exactly two, three or four transcription and reprogramming factor genes, each gene separated by a 2a self-cleavage peptide sequence, c) a spleen focus-forming virus promoter, and d) a post-transcriptional regulatory element Wpre, with or without an anti-apoptotic factor gene. A method for generating integration-free induced pluripotent stem cells, the method comprising: a) providing target cells, b) providing one or more than one vector according to the present invention, c) transducing or transfecting the target cells with the one or more than one vector, and d) culturing the transduced or transfected cells in a cell culture, thereby generating integration-free induced pluripotent stem cells.

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).