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: Described are antigen specific and antigen non-specific means of suppressing development of Type 1 Diabetes in a mammal through administration of exosomes, microvesicles or apoptotic bodies from monocytic lineage cells that have been reprogrammed by contact with mesenchymal stem cells and/or mesenchymal stem cell conditioned media. In one embodiment, the invention provides administration of exosomes that have been generated from monocytic cells that have been loaded with tolerogenic antigens and/or epitopes. In another embodiment the invention provides administration of allogeneic myeloid derived exosomes that are loaded with tolerogenic antigens. In another embodiment the invention provides means of stimulating exosome release in vivo from allogeneic cells that have been administered to the patient in need of treatment.

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 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: Disclosed herein are methods of reducing pathological inflammation and effects thereof through administration of tissues associated with regenerative and/or tolerogenic activity. In some embodiments, such tissues can include placental, ocular, testicular, and osseous tissues. Augmentation of therapeutic effects of said tissues may be achieved through contact with Injury Mimetics.

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: Disclosed are means of inducing and accelerating neurological recovery subsequent to a stroke through administration of amniotic fluid derived stem cells. In one embodiment stem cells are isolated from amniotic fluid and expanded under conditions allowing for expression of SSEA3, SSEA4, Tra1-60, Tra1-81, Tra2-54, Oct-4 and CD105. Said cells are subsequently administered into a patient having undergone a stroke, so as to induce direct regeneration (through transdifferentiation and replacement of neural tissue), as well as indirect regeneration (through production of growth factors that augment endogenous regenerative mechanisms while inhibiting degenerative mechanisms). In some embodiments factors produced by said amniotic fluid stem cells may be utilized instead of cells themselves. Said factors may include proteins, peptides, conditioned media, exosomes, or microvesicles.

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: 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: 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: 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: Disclosed are methods and compositions related to treatment, amelioration or prevention of cachexia or inflammation related to cachexia in a subject. As disclosed, cachexia or inflammation related to cachexia can be treated, ameliorated or prevented by the administration of an effective amount of a composition including immune-modulating fibroblasts to the subject.

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: 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 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: 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: 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: Embodiments of the disclosure include methods and compositions related to prevention of spontaneous miscarriage in an individual. In certain cases, fibroblasts are provided in an effective amount to an individual in need thereof. Alternatively or in addition, lymphocytes are obtained, cultured with fibroblasts, and provided to an individual. Fibroblasts may modulate an immune response in an individual, thereby reducing the risk of spontaneous miscarriage.

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: Disclosed are methods, means and compositions of matter useful for treatment of heart failure, and/or post infarct pathological remodeling 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 cardiac fibrotic cells. In other embodiments, said immune cells provide antifibrotic activity to induce suppression of cardiac fibrosis. In other embodiments, said immune cells provide for growth factors to enhance cardiac regeneration.