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.

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: Disclosed are compositions and methods of treating muscular dystrophies, including Duchenne Muscular Dystrophy (DMD) through administration of fibroblasts and modified fibroblasts systemically and locally. In certain embodiments, fibroblast cells are utilized for replacement of dystrophin through fusion and/or other means of horizontal gene transfer. In other embodiments, the disclosure teaches the use of fibroblasts for reduction of inflammatory reactions and/or immunological reactions which propagate and enhance myodestructive aspects of Duchenne Muscular Dystrophy. In other embodiments, fibroblasts are utilized as vectors for gene therapy and/or gene modifications approaches.

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 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: Disclosed are methods and compositions comprising fibroblasts and/or products derived thereof for the inhibition and/or treatment of addiction of any kind, such as opioid addiction. In some embodiments, methods comprise treating a patient addicted to opioids by administering a fibroblast population at a concentration sufficient for suppression of addiction-associated brain damage. In some embodiments, the fibroblasts express CD31 and/or CD73 markers. In some embodiments, fibroblasts are used to endow neuronal regeneration in order to overcome changes in the brain associated with addiction. Some embodiments relate to the stimulation of hippocampal regeneration subsequent to addiction induced damage.

Abstract: The present disclosure concerns methods and compositions for differentiating cells, including adipose cells, into chondrocyte-like cells via in vitro, ex vivo, and/or in vivo mechanical strain. In particular aspects, adipose cells or re-differentiated adipose cells that are chondrocyte-like cells, are delivered to a joint or are shaped into cartilage. In some embodiments, the adipose cells may be delivered to a joint, such as an intervertebral disc, following which the cells differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. In certain aspects, the cells prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

Abstract: The present disclosure concerns methods and compositions for differentiating cells, including adipose cells, into chondrocyte-like cells via in vitro, ex vivo, and/or in vivo mechanical strain. In particular aspects, adipose cells or re-differentiated adipose cells that are chondrocyte-like cells, are delivered to a joint or are shaped into cartilage. In some embodiments, the adipose cells may be delivered to a joint, such as an intervertebral disc, following which the cells differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. In certain aspects, the cells prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

Abstract: The present disclosure concerns at least methods and compositions for repairing and/or regenerating a disc of an individual in need thereof. In certain embodiments, an individual that is known to have or suspected to have or at risk for having a degenerated disc is provided a therapeutically effective amount of nucleus pulposus cells, one or more components from the nucleus pulposus, conditioned medium generated from nucleus pulposus cells, and additionally may also be provided fibroblasts, platelet rich plasma (PRP), SOX9 (protein or nucleic acid), and/or Tie2+ cells, for example.

Abstract: The present invention concerns methods and compositions for differentiating cells, including human fibroblasts, into chondrocyte-like cells via in vivo mechanical strain. In particular aspects, fibroblasts are delivered to a joint, such as an intervertebral disc, following which the fibroblasts differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. The fibroblasts that do not differentiate to chondrocytic cells because of the location of the cells, as in the fissures of annulus, or other biomechanical and biochemical micro-environment factors, may produce fibrous matrix molecule(s) in aiding tissue repair and regeneration in both nucleus pulposus and annulus fibrosus. In certain aspects, the fibroblasts prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

Abstract: Disclosed are compositions of matter, cells, protocols and procedures useful for augmentation of one or more therapeutic activities of fibroblast cellular populations. In one embodiment fibroblasts are pretreated with growth factor-comprising composition(s), wherein the growth factor(s) may be cytokines, peptides, and/or proteins. In another embodiment fibroblasts are cultured with platelet rich plasma and/or derivatives from platelet rich plasma. In another embodiment, fibroblasts are cultured under hypoxic conditions prior to administration to an individual. The disclosure further provides means of assessment of fibroblast activity in vitro, including wound repair assay and cytokine production, for example.

Abstract: Methods and systems are provided of providing an incentive to a player of a game on a computing device comprising the steps of receiving a player submission, determining whether or not the player submission is valid, if the player submission is valid, presenting the player with positive feedback, retrieving one or more player parameters from a data repository, determining whether or not the player is eligible for one or more awards, based at least in part on the one or more player parameters, if the player is eligible for at least one award, presenting the player with the one or more awards, and if the player submission is not valid, presenting the player with negative feedback.

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: Methods and systems are provided of presenting a game on user interface of a computing device including the steps of resenting a player with a countdown timer, a letter from the alphabet, and one or more instructions where the player is expected to enter the name of an artist beginning with the letter from the alphabet, receiving a player submission, if the countdown timer has not elapsed, determining whether or not the player submission is valid, and if the player response is valid, awarding points to the player for a matched a name wherein the points are equal to the amount of time remaining.

Abstract: The present disclosure concerns methods and compositions for differentiating cells, including adipose cells, into chondrocyte-like cells via in vitro, ex vivo, and/or in vivo mechanical strain. In particular aspects, adipose cells or re-differentiated adipose cells that are chondrocyte-like cells, are delivered to a joint or are shaped into cartilage. In some embodiments, the adipose cells may be delivered to a joint, such as an intervertebral disc, following which the cells differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. In certain aspects, the cells prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

Abstract: The present invention concerns methods and compositions for differentiating cells, including human fibroblasts, into chondrocyte-like cells via in vivo mechanical strain. In particular aspects, fibroblasts are delivered to a joint, such as an intervertebral disc, following which the fibroblasts differentiate into chondrocyte-like cells to treat dysfunction of cartilage therein, including to repair degenerated discs, for example. The fibroblasts that do not differentiate to chondrocytic cells because of the location of the cells, as in the fissures of annulus, or other biomechanical and biochemical micro-environment factors, may produce fibrous matrix molecule(s) in aiding tissue repair and regeneration in both nucleus pulposus and annulus fibrosus. In certain aspects, the fibroblasts prior to delivery to the individual are managed in the absence of growth factors, in vitro mechanical strain, and/or matrix molecules, for example.

Abstract: Embodiments of the invention encompass the ex vivo production of cartilage from chondrocytes differentiated from fibroblasts or stem cells. In particular embodiments, fibroblasts are subjected to conditions to produce chondrocytes in the form of cartilage tissue, for example cartilage having a desired shape. In at least some embodiments, a mold for the desired shape of the cartilage is produced from imaging of a body region of an individual in need thereof, and the fibroblasts are seeded in the mold with particular conditions.