Abstract: In some aspects, disclosed herein are methods and compositions for treatment or prevention of cerebral palsy using fibroblasts or derivatives thereof. Disclosed herein are fibroblasts and derivatives thereof capable of inducing neurogenesis and/or reducing inflammation in a subject. In some cases, the disclosed methods comprise use of conditioned fibroblasts. Fibroblasts may be conditioned with agents capable of enhancing therapeutic efficacy, for example oxytocin and/or human chorionic gonadotrophin (hCG).

Abstract: Disclosed herein are methods and compositions for modulation of telomere length in cells. Aspects are directed to reduction in telomere shortening rate, stabilization of telomere shortening, and/or telomere elongation using fibroblasts or fibroblast-derived products. In some cases, provided are methods for treatment of telomere-associated conditions using fibroblasts or fibroblast-derived products. Fibroblasts may be provided to modulate telomere length in cells of a subject, thereby treating a telomere-associated condition such as, for example, cancer, aging, or idiopathic pulmonary fibrosis.

Abstract: Embodiments of the disclosure concern reducing deleterious effects of inflammatory cytokines, such as interleukin-17, by providing to an individual with inflammation or at risk for inflammation an effective amount of fibroblasts and/or fibroblast derivatives thereof that reduce production of IL-17 from immune cells, that suppress responsiveness of cells to IL17, and/or that suppress generation of Th17 cells.

Abstract: Disclosed are means of suppressing production of the inflammatory cytokine TNF-alpha through contact-dependent and contact-independent means by fibroblast populations and products and/or derivatives of fibroblast populations. In one embodiment, fibroblasts are cultured under conditions allowing proliferation of said fibroblasts, wherein said proliferative status of fibroblasts correlates with the ability to directly suppress TNF-alpha production, and/or to release one or more factors capable of suppressing TNF-alpha production. In one embodiment, fibroblasts are used for treatment of inflammatory diseases by their ability to suppress TNF-alpha production. In other embodiments, conditioned media and/or exosomes of said fibroblasts are utilized to treat inflammatory diseases by their ability to suppress TNF-alpha production.

Abstract: Embodiments of the disclosure include methods and compositions useful for treating cancer in an immunogenic manner so as to elicit local tumor regression, while priming systemic immunity. In one embodiment, there is expansion of tumor-specific immune cells through administration of fibroblasts, either natural or modified in an intratumoral and/or peritumoral manner. In other embodiments, manipulation of a local tumor microenvironment is achieved by injections of immune-modulating fibroblasts to facilitate expansion of immune effector cells, which are subsequently re-stimulated in the periphery by antigenic exposure. In another embodiment, agents are provided that allow for systemic derepression of immunity, while optionally augmenting ability of immune effector cells to expand and kill tumor cells.

Abstract: Disclosed is the utilization of cannabidiol, either through systemic and/or local administration, for use as an adjuvant in treatments of disc degenerative disease. In some embodiments, cannabidiol is utilized to enhance therapeutic and/or regenerative activities of fibroblasts. In other embodiments, cannabidiol is utilized to augment reparative effects of other regenerative cells including monocytes, mesenchymal stem cells, and/or hematopoietic stem cells. In some embodiments cannabidiol is utilized in the culture media of regenerative cells prior to administration of said cells.

Abstract: 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.

Abstract: In some aspects, disclosed herein are methods and compositions for treatment of inflammatory bowel disease using fibroblasts or derivatives thereof. Disclosed herein are compositions having tolerogenic properties. Compositions of the present disclosure include fibroblasts, activated fibroblasts, fibroblast apoptotic bodies, and fibroblast exosomes. Methods of the present disclosure include, in some cases, providing fibroblasts or derivatives thereof to a subject to treat an inflammatory bowel disease. In some cases, dendritic cells are cultured with fibroblasts and provided to a subject to treat an inflammatory bowel disease.

Abstract: Described are means of generating immunological compositions that are universally applicable for induction of immunity to neoplasia regardless of histological origin of tissue. Certain methods concern fibroblasts that are manipulated or dedifferentiated in a manner to induce expression of tumor associated antigens including cancer testis antigens. These cells are used as a source of antigenic stimuli for creation of a cellular vaccine, and/or an exosome vaccine, and/or a lysate-based vaccine.

Abstract: The disclosure provides means, methods, and compositions of preventing, reducing, and treating kidney failure through the administration of fibroblasts, modified fibroblasts, and/or products derived from fibroblasts. The disclosure may also concern administration of fibroblasts prior to, concurrent with, or subsequent to administration of a nephrotoxic agent results in production of renal function. In some embodiments, fibroblasts are enhanced for augmentation of nephron-regenerative properties through culture under means including hypoxia, histone deacetylase inhibitor treatment, oxytocin, and/or DNA methyltransferase inhibitors.

Abstract: Embodiments of the disclosure include methods of increasing the efficacy of a fibroblast cell therapy for any medical condition, including degenerative disc disease, by providing at least one anti-inflammatory composition, exosomes and/or apoptotic bodies, stem cells, or a combination thereof; and administering the fibroblast cell therapy. The anti-inflammatory composition may comprise a composition that inhibits and/or reduces TNF-alpha, such as melatonin.

Abstract: Embodiments of the disclosure concern methods and compositions related to cancer treatment for an individual utilizing recombinant fibroblast cells that comprise one or more activities that are endothelial cell-like. The cells are delivered to a tumor microenvironment following which their death results in destabilization of the tumor vasculature. In particular embodiments, the fibroblast cells recombinantly express one or more of ETV2, FOXC2, and FLI1.

Abstract: Embodiments of the disclosure include methods and compositions for treating neurological disorders by stimulating regenerative and anti-inflammatory activity of fibroblasts. In specific embodiments, fibroblasts are administered to an individual with one or more inhibitors of NFkappaB, including minocycline and/or analogues thereof. In specific cases, methods are utilized herein to treat or prevent central nervous system injury, such as chronic injuries including chronic traumatic encephalopathy.

Abstract: The disclosure includes embodiments for utilizing fibroblasts derived from cancer patients and generating “de novo” tumor specific cancer cells and cancer stem cells. The cells may be used as a source of one or more patient-specific antigens for generating one or more personalized tumor vaccines.

Abstract: Disclosed are means, methods, and compositions of matter useful for treatment of pervasive developmental disorders. The treatment includes the use of fibroblasts, modified fibroblasts, and derivatives thereof for reduction of neuroinflammation and/or gastrointestinal inflammation in a patient in need of treatment, such as having a pervasive developmental disorder. Fibroblasts, modified fibroblasts, and derivatives thereof may be administered at a frequency and concentration sufficient to reduce interleukin-17 production in the gut of patients with autism spectrum disorder.

Abstract: Embodiments of the disclosure include methods and compositions related to modulation of bone using particular fibroblasts. The modulation includes reducing osteoclast activity and/or activation and/or stimulating osteoblast activity. In particular cases, bone is modulated in an individual with a bone condition, such as osteoporosis. Particular fibroblasts may be delivered to reduce inflammatory cytokine production including RANK ligand.

Abstract: Embodiments of the disclosure encompass methods and compositions related to the ability of RNA to enhance therapeutic activity of fibroblasts. In some embodiments, administration of double stranded RNA is performed through providing polyinosinicpolycytidylic acid (poly (I:C)) or a derivative thereof at a concentration sufficient to induce therapeutic properties and/or to augment therapeutic properties onto said fibroblasts. In one embodiment, enhanced therapeutic activity comprises augmentation of fibroblast migratory activity; efficacy for angiogenesis; efficacy for immune modulation; differentiation ability; production of one or more trophic factors; and/or the ability to resist apoptosis.

Abstract: Embodiments of the disclosure include methods and compositions related to selecting donor fibroblasts suitable for use in an allogeneic recipient individual. The methods and compositions encompass identifying expression of one or more human leukocyte antigens (HLA) and in some cases expression of one or more other factors, including regenerative factors.

Abstract: Embodiments of the disclosure concern methods and compositions for enhancing therapeutic efficacy of fibroblast therapy for an individual in need thereof. The disclosure concerns administering to the individual one or both of interleukin-2 (IL-2) and one or more anti-CD3 agents to enhance efficacy of the fibroblast therapies. In specific cases, the IL-2 is provided to the individual at particular low doses, and the anti-CD3 agent may be a monoclonal antibody.

Abstract: Disclosed are compositions, systems and methods comprising a regenerative fibroblast cell, population or subsets thereof possessing regenerative activity useful for treatment of various degenerative diseases. In one embodiment, the disclosure provides fibroblasts with enhanced proliferative potential based on enrichment for CD105 and/or CD117 markers. In one embodiment, fibroblasts possessing CD105 and/or CD117 markers are further enriched for the property of rhodamine 123 efflux.