Abstract: Disclosed are methods, means, and compositions of matter useful for the stimulation of angiogenesis directly by administration of membrane vesicles, such as fibroblast-derived exosomes, and/or through induction of angiogenic cytokines from blood cells contacted with fibroblast-derived exosomes. The invention provides means of treating conditions in which angiogenesis is beneficial through local or systemic administration of exosomes, including those derived from fibroblasts, wherein the fibroblasts are cultured under basal conditions or conditions of hypoxia. In other embodiments exosomes derived from fibroblasts are utilized to augment endogenous regenerative processes, such as hematopoiesis, angiogenesis and neurogenesis, as well as augment regenerative processes stimulated by administration of exogenous therapeutics such as cells, growth factors, or genes.

Abstract: Embodiments of the disclosure encompass methods and compositions for treatment of cancer utilizing fibroblasts that have been modified to enhance their ability to deliver one or more anti-cancer agents to an individual in need thereof. In particular embodiments, the fibroblasts have been modified to express one or more chemokine receptors and/or have been exposed to hypoxia to enhance their ability to home to cancer cells. In specific cases the modified fibroblasts are engineered to encompass an oncolytic virus as a tumor inhibitory agent.

Abstract: Embodiments of the disclosure encompass methods and compositions for treatment of cancer utilizing fibroblasts that have been modified to enhance their ability to deliver one or more anti-cancer agents to an individual in need thereof. In particular embodiments, the fibroblasts have been modified to express one or more chemokine receptors and/or have been exposed to hypoxia to enhance their ability to home to cancer cells. In specific cases the modified fibroblasts are engineered to encompass an oncolytic virus as a tumor inhibitory agent.

Abstract: The present disclosure provides means of regenerating/restoring aged and/or damaged tissue or treating a medical condition by providing an extracorporeal circuit containing cells, including fibroblasts or dedifferentiated fibroblasts. that are in contact with plasma but not blood cells extracorporeally in a manner allowing for exchange of factors between a subject and an extracorporeally residing mass of cells. The disclosure provides means of titrating factors produced by the extracorporeal regenerative cell mass, thus allowing for a regenerative effect.

Abstract: Disclosed are methods, means, and compositions of matter useful for the stimulation of angiogenesis directly by administration of membrane vesicles, such as fibroblast-derived exosomes, and/or through induction of angiogenic cytokines from blood cells contacted with fibroblast-derived exosomes. The invention provides means of treating conditions in which angiogenesis is beneficial through local or systemic administration of exosomes, including those derived from fibroblasts, wherein the fibroblasts are cultured under basal conditions or conditions of hypoxia. In other embodiments exosomes derived from fibroblasts are utilized to augment endogenous regenerative processes, such as hematopoiesis, angiogenesis and neurogenesis, as well as augment regenerative processes stimulated by administration of exogenous therapeutics such as cells, growth factors, or genes.

Abstract: Embodiments of the disclosure include methods and compositions for use of prepared fibroblasts and/or conditioned media therefrom. In particular embodiments, the prepared fibroblasts have enhanced regenerative and may have an increase in secretion of one or more cytokines and/or growth factors; may have an increase in anti-apoptotic activity; and/or may have a modulated immunogenicity. In specific embodiments, the fibroblasts are prepared by exposure to hypoxia and/or carbon monoxide.

Abstract: Embodiments of the disclosure include methods and compositions for treatment of lung disease, including at least chronic obstructive pulmonary disease (COPD). In particular cases, fibroblasts (including activated fibroblasts) and/or exosomes thereof are provided to an individual for the treatment of COPD. In particular cases the fibroblasts are activated and/or express one or more particular markers.

Abstract: Embodiments of the disclosure include methods and compositions for treatment of lung disease, including at least chronic obstructive pulmonary disease (COPD). In particular cases, fibroblasts (including activated fibroblasts) and/or exosomes thereof are provided to an individual for the treatment of COPD. In particular cases the fibroblasts are activated and/or express one or more particular markers.

Abstract: Embodiments of the disclosure include methods and compositions for use of prepared fibroblasts and/or conditioned media therefrom. In particular embodiments, the prepared fibroblasts have enhanced regenerative and may have an increase in secretion of one or more cytokines and/or growth factors; may have an increase in anti-apoptotic activity; and/or may have a modulated immunogenicity. In specific embodiments, the fibroblasts are prepared by exposure to hypoxia and/or carbon monoxide.

Abstract: Described are means, methods, and compositions useful for treatment of multiple sclerosis through the utilization of fibroblasts and/or derivatives thereof to concurrently stimulate regenerative processes while inducing a protolerogenic immune modulatory program. In certain embodiments, fibroblasts are selected for the concurrent properties of immune modulation and regeneration by enrichment for CD73 expressing fibroblasts. In particular embodiments, stimulation of regeneration implies activation of endogenous neural progenitor cells. In some embodiments, stimulation of regeneration implies induction of remyelination. The utilization of fibroblasts as a superior source for immune modulation, prevention of immune mediated pathology, and activation of T regulatory cells is provided within the context of multiple sclerosis.

Abstract: Embodiments of the invention concern the regeneration of chondrocytes and cartilage-type cells. In certain embodiments, one or more genes are employed for the regeneration of chondrocytes and cartilage-type cells. In particular embodiments, one or more gene therapy regimens are employed for the regeneration of chondrocytes and cartilage-type cells. In particular aspects, embodiments concern cartilage repair, such as articular cartilage repair. More particularly, embodiments for the disclosure concern using gene therapy for the attraction, generation and/or regeneration of chondrocytes or other cartilage-type cells and/or the generation and/or repair of cartilage tissue. In specific embodiments of the disclosure, gene therapy is provided that is capable of attracting and/or generating desired cells in vivo.

Abstract: In some aspects, disclosed are methods and compositions for disc regeneration and/or repair using one or more components from conditioned media from fibroblasts. In certain cases, conditioned media is obtained from fibroblasts stimulated with one or more opioid receptor antagonists and one or more toll-like receptor agonists. Conditioned media from fibroblasts may be provided in an effective amount to an individual in need thereof.

Abstract: Embodiments of the disclosure encompass methods of increasing insulin sensitivity in an individual in need thereof. The increase in insulin sensitivity may derive from individuals that have diabetes, aging, low grade inflammation, obesity, pregnancy, metabolic syndrome X, congenital abnormality or a combination thereof. In specific embodiments, the methods encompass providing to an individual an effective amount of fibroblast cells of certain kinds.