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 disclosure include methods and compositions related to treatment and prevention of an excess of cytokines in an individual using fibroblasts or fibroblast-derived microvesicles. In particular embodiments, there are methods and compositions for treating and preventing toxicities in an individual that may be the result of cytokine release syndrome. In specific cases, an individual is treated for cytokine release syndrome with fibroblasts having one or more specific markers.

Abstract: The present disclosure is directed to methods and compositions of engineered fibroblast cells with one or more types of modifications such that the cell has a reduced immune response either alone, in association with other immune cells, or both. In some embodiments, one or more targets are modified on the surface of the cell. In specific embodiments, engineered cells to be used in cellular transplantation therapy are modified to have reduced immunogenicity.

Abstract: Disclosed are methods, compositions of matter, and means of treatment or prophylaxis using fibroblasts possessing regenerative properties for the treatment of brain injuries including stroke, transient ischemic injuries, chronic traumatic encephalopathy, traumatic brain injury, and tauopathies. Embodiments of the disclosure administer fibroblasts with regenerative properties either systemically, locally, or a combination of the two prior to, concurrent with, or subsequent to a brain injury. In some embodiments of the disclosure fibroblasts or products thereof, are administered intranasally, intrathecally, and/or intravenously.

Abstract: Embodiments of the disclosure concern methods and compositions related to treatment of cachexia or inflammation related thereto. In specific embodiments, cachexia or inflammation related thereto is to treated or prevented by the administration of fibroblasts. In specific embodiments, the fibroblasts are amniotic-derived fibroblasts.

Abstract: Embodiments of the disclosure pertain to the treatment of diabetes through replacement of insulin producing cells. In specific embodiments, the disclosure encompasses the use of cellular adjuvants to enhance survival, engraftment and tolerogenesis of insulin-producing cells. In certain cases the disclosure concerns the manipulation of a hepatic microenvironment to promote immunological tolerance at an enhanced level to allow for integration of allogeneic insulin-producing cells. Particular embodiments utilize fibroblasts to enhance immunological tolerance for insulin-producing cells upon engraftment.

Abstract: Embodiments of the disclosure encompass methods and compositions using fibroblasts for stimulating regeneration in a first tissue site in an individual, comprising the step of administering at least one regenerative composition to a second tissue site, wherein the second tissue site comprises the same tissue type as the first tissue site in the individual. The first and second sites are at different locations in the individual, in particular embodiments. Particular embodiments comprise administering one or more compositions to an individual at a different anatomical site than the site that is in need, such as a joint.

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: The present disclosure is directed to systems, methods, and compositions for functional interaction of fibroblasts with one or more types of immune cells such that the interaction results in modification to the fibroblasts, the one or more types of immune cells, or both. In some embodiments, one or more certain agents are also utilized during the interaction or in lieu of one of the types of cells. In specific embodiments, cells to be used in cellular transplantation therapy are modified to have reduced immunogenicity.

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: Embodiments of the disclosure encompass methods and compositions related to bioprinting processes that utilize fibroblasts in a structural and/or functional capacity. In specific embodiments, fibroblasts or cells derived therefrom are utilized in a bioprinting process. Cells derived from fibroblasts include cells that derive from fibroblasts that were dedifferentiated and then re-differentiated into cells of a desired phenotype for use in the bioprinting process. Such bioprinting processes may produce specific tissues, organoids and/or organs.

Abstract: Embodiments of the disclosure include methods and compositions for treatment or prevention of pain in an individual. In specific embodiments, the methods and compositions encompass fibroblasts and/or fibroblast derivatives for the treatment of any kind of pain, including back pain. In particular aspects, exosomes and/or lysate and/or conditioned media from the fibroblasts are provided to an individual in need thereof.

Abstract: Embodiments of the disclosure include methods and compositions related to preparation of fibroblasts for use of treatment and prevention of a degenerative disc in an individual. In particular cases, fibroblasts are subject to de-differentiation that results in enhancement of their therapeutic activity and such methods include exposure of the fibroblasts to one or more agents and/or conditions.

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: 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: Embodiments of the disclosure include methods and compositions related to fibroblasts that express at least one chimeric antigen receptor (CAR). In specific embodiments, the chimeric antigen receptor has an antigen-specific targeting region that targets a tumor or pathogen antigen and that comprises an intracellular domain that upon signal through the chimeric antigen receptor is able to endow the fibroblasts with the ability to induce an immune response in an individual. In other embodiments, activity of CAR-expressing cells of any kind is enhanced through administration of fibroblasts that may or may not themselves express one or more CARs.

Abstract: Embodiments of the disclosure encompass T-regulatory cells for use in treating disc degenerative disease. The T-regulatory cells may be autologous or allogeneic to the individual being treated. In specific embodiments, the T-regulatory cells express certain markers and are derived from certain sources.

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 on 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 include methods and compositions for disc repair in a mammal using conditioned media (and/or one or more components therefrom) from fibroblasts that have been de-differentiated and cultured optionally with one or more particular conditions and/or compositions. In specific cases, fibroblasts that have been de-differentiated are exposed to hypoxia, histone deacetylase inhibitor(s), DNA methyltransferase inhibitor(s), or a combination thereof, and the conditioned media therefrom is provided in an effective amount to an individual.

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.