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: 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: 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 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.

Abstract: Disclosed are compositions of matter, therapeutic interventions, and combination treatments for preventing and/or reducing colitis. In one embodiment, administration of specific mesenchymal stem cell subsets into a patient suffering from colitis, wherein said mesenchymal stem cells possess enhanced ability to stimulate T regulatory cells. In one embodiment the patient is administered a composition capable of altering the colonic microenvironment prior to administration of stem cells. In other embodiments microbiome associated metabolites are administered prior to, concurrent with, or subsequent to stem cell administration. In some embodiments treatment of colitis is accomplished by stimulation of immune modulation together with mesenchymal stem cell administration.

Abstract: Novel populations of canine derived stem cells useful for treatment across allogeneic barriers. The stem cells can be of mesenchymal lineage optimized to possess enhanced proliferative activity in vitro and in vivo without significant loss of therapeutic functionality. Said therapeutic activities include angiogenesis, stimulation of growth factor production, antifibrotic effects, neurogenesis, immune modulation, and antiapoptotic effects.

Abstract: Compositions of matter, interventions and protocols for treatment of degenerative disc disease through administration of B regulatory cells and/or stimulation of B regulatory cell generation. B regulatory cells can be administered intradiscally in order to support regenerative processes of endogenous nucleus pulposus cells or administered regenerative cells. Peri-spinal administration of B regulatory cells can alter the microenvironment to support activity of therapeutic cells capable of increasing extracellular matrix quality and quantity. B regulatory cells can be expanded in vitro from progenitor cells including induced pluripotent stem cells, or may be utilized from adult progenitor sources such as peripheral blood, cord blood, and bone marrow.

Abstract: Methods, systems, and compositions of matter for detection, analysis and treatment of biological, chemical and radiation exposure using artificial intelligence-based systems including fuzzy logical and/or machine learning. A system capable of compiling physical, biochemical, hematological, psychological and neural datapoints, analyzing said data points and creating actionable therapeutic interventions in a graded manner based on invasiveness and probability of success. Optimized biological intervention to chemical, radiation and biochemical threats using stem cells, T regulatory cells and induced pluripotent stem cells.

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.