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: Disclosed are means, methods and compositions of matter useful for prevention and/or reversion of type 1 diabetes by upregulation of myeloid suppressor cell activity in a mammal suffering from and/or at risk of developing type 1 diabetes. In one embodiment the invention teaches administration of immune cells that have been conditioned by exposure to regenerative cells, and/or cultured in the presence of factors produced from regenerative cells. In one embodiment said regenerative cells are umbilical cord derived mesenchymal stem cells. In one embodiment, immune cells that have been exposed to said regenerative cells are administered together with agents known to enhance myeloid suppressor cell activity. In another embodiment immune cells are administered together with exogenous myeloid suppressor cells.

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: In some aspects, disclosed herein are methods and compositions for treatment of sclerosing cholangitis using fibroblasts or derivatives thereof. The disclosed compositions include fibroblasts, engineered fibroblasts, exosomes obtained from fibroblasts, and conditioned media derived from fibroblasts. Methods of the present disclosure include providing fibroblasts to a subject to treat sclerosing cholangitis in the subject. Fibroblasts of the disclosure include fibroblasts capable of reducing inflammation in a subject. In certain aspects, fibroblasts are cultured with activating agents prior to therapeutic administration.

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 treatments of subconcussive and/or concussive brain damage by administering fibroblasts and/or fibroblasts cultured with one or more types of immunocytes. In one specific embodiment fibroblasts are cultured with monocytes in the presence of patient-specific T cells, and subsequently the T cells are re-administered into the patient. In one particular embodiment, products derived from fibroblast-immunocyte mixtures are comprised of cellular lysate, apoptotic bodies, exosomes, and/or other microvesicles. In one embodiment, the fibroblast cells and/or products derived from the fibroblast cells are administered subsequent to one or multiple head injuries. In other embodiments, products are administered in combination with neurorestorative and/or neuroprotective interventions.

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: 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: Disclosed are means, methods and compositions of matter useful for suppressing pathological production of new blood vessels in conditions such as cancer and wet macular degeneration. In one embodiment the invention provides silencing of NR2F6 using nucleic acid based approaches such as RNA interference, antisense oligonucleotides, or DICER. In another embodiment, the invention teaches the administration of small molecule NR2F6 inhibitors as means of selectively inhibiting pathological but not healthy angiogenesis.

Abstract: Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors. In one embodiment further immunization is performed subsequent to removal of said blocking factors in order to allow for enhancement of adaptive immune responses.

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: Disclosed are means, methods, and compositions of matter useful for enhancement of dendritic cell activity. In one embodiment the invention provides the use of GABA agonists such as homotaurine for stimulation of dendritic cell activity. In one embodiment said dendritic cell activity is enhancement of natural killer cell activity and/or of T cell activity. In one embodiment NK cell activity is ability to induce cytotoxicity in neoplastically transformed cells, whereas T cell activity is either cytokine production for CD4 cells or cytotoxicity for CD8 cells.

Abstract: Disclosed are treatment methods, protocols, and compositions of matter useful for treatment of kidney failure. The invention discloses, in one embodiment, administration of immune cells that have been reprogrammed by co-culture with regenerative cells. In one embodiment said regenerative cells are umbilical cord derived mesenchymal stem cells and said immune cells are peripheral blood mononuclear cells. In one embodiment cells are cultured together in the presence of interleukin 2 and/or an mTOR inhibitor. In one embodiment said cells are cultured together in the presence of an anti-CD3 and/or anti-CD28 antibody.

Abstract: Disclosed are methods of ameliorating, inhibition, and/or reversing diabetes utilizing immune cells that have been reprogrammed ex vivo by contact with regenerative cells. In one embodiment said reprogrammed immune cells comprise peripheral blood mononuclear cells obtained from the patient in need of treatment wherein said cells are endowed with properties of immune modulation, and/or suppression of inflammation, and/or restoration of insulin sensitivity, and/or pancreatic regeneration. In one embodiment regenerative cells used for reprogramming are mesenchymal stem cells. In one particular embodiment said cells are umbilical cord derived mesenchymal stem cells. Culture of peripheral blood mononuclear cells together with said regenerative cells is performed in the presence of interleukin-2 and/or an mTOR inhibitor. In one embodiment said mTOR inhibitor comprises rapamycin and/or a derivative thereof.

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 methods, means and compositions of matter useful for treatment of liver failure using ex vivo reprogrammed immune cells. In one embodiment, cells of the recipient (autologous) are cocultured with a regenerative cell population alone or in the presence of one or more adjuvants. Said adjuvants enhance transfer of regenerative activity from said mesenchymal stem cells to said immune cells. In one embodiment said ex vivo reprogrammed immune cells are capable of inducing death or inactivation of hepatic stellate cells. In other embodiments, said immune cells provide antifibrotic activity to induce suppression of liver cirrhosis. In other embodiments, said immune cells provide for growth factors to enhance hepatic regeneration.