Abstract: Cellular modifications useful for enhancing migratory potential of T regulatory cells that have been derived from inducible pluripotent stem cells. In one embodiment said inducible pluripotent stem cells are gene edited for insertion or deletion of cytoskeletal and motility associated genes in order to increase migration ability as well as deformability of cells in a manner allowing for increased extravasation and mobility. In other embodiments inducible pluripotent stem cell derived T regulatory cells are gene edited at the level of T Regulatory cell progenitor stage.

Abstract: The invention provides methods of inducing immunological tolerance to a transplanted cellular population or organ by creating and administering a “veto-like” cell originating from the identical genetic background of the organ donor. In one embodiment said artificially generated veto cell is a dendritic cell population possessing molecules associated with tolerance induced in natural anatomical locations such as the placenta, the testis, or the eye. In one embodiment dendritic cells resistant to maturation are generated from pluripotent stem cells that have been gene edited to lack genes needed for acquisition of antigen presenting properties such as relB, NF-kappa B and transporter associated protein. In another embodiment immature dendritic cells are gene edited/transfected to express tolerance associated molecules such as interleukin-10, interleukin-35, Fas ligand, TRAIL, TGF-beta, HLA-G and arginase.

Abstract: The present disclosure provides means of inhibition and/or treating aneurysms and other degenerated blood vessels through administration of regenerative cell derived exosomes, and/or regenerative cell derived apoptotic bodies. In one particular embodiment vessel regeneration is increased through administration of stem cell exosomes/or stem cell apoptotic bodies. Other embodiments include regeneration of vessels prone to aneurysms, repairing aneurysms of vessels, or acceleration of endothelialization after stent placement. Provided within the invention are methods of rejuvenating properties of said vessels associated with physiological health, examples of which include appropriate production of anti-coagulating/clotting factors, control of angiogenesis, and appropriate revascularization of injured tissue.

Abstract: Disclosed are methods and means of optimizing health of a subject during space travel comprising real time monitoring and intervention guided by automated and/or semiautomated means driven by a machine learning artificial intelligence-based system. In one embodiment the invention discloses the integration of genetic factors, biological properties, microbiome diversity, regenerative activity, and real time physiological changes in order to provide optimum interventions which result in increased health upon return from the space mission, as well as provide ability for said astronaut to endure space travel of increased durations.

Abstract: Disclosed are means, methods and compositions of matter useful for stimulation of immunity to tumor antigens through isolation of dendritic cell exosomes from dendritic cells that have been pulsed with said tumor antigens and/or pulsed dendritic cells that have been gene silenced/gene edited for immune suppressive genes. In one embodiment said tumor antigen is survivin and said immune suppressive genes include interleukin-10, interleukin-35, TGF-beta and interleukin-13. In some embodiments dendritic cells are further transfected with immune stimulatory genes including interleukin-2, interleukin?12, interleukin-15 and interleukin-18.

Abstract: Disclosed are methods and compositions comprising fibroblasts and/or products derived thereof for the inhibition and/or treatment of addiction of any kind, such as opioid addiction. In some embodiments, methods comprise treating a patient addicted to opioids by administering a fibroblast population at a concentration sufficient for suppression of addiction-associated brain damage. In some embodiments, the fibroblasts express CD31 and/or CD73 markers. In some embodiments, fibroblasts are used to endow neuronal regeneration in order to overcome changes in the brain associated with addiction. Some embodiments relate to the stimulation of hippocampal regeneration subsequent to addiction induced damage.

Abstract: Disclosed are means of generating organs or organoids utilizing three-dimensional bio-printing processes. In one embodiment said organ is a pancreas or pancreas-like organ useful for the treatment of diabetes, wherein said bioprinted pancreas possesses enhanced regenerative activity, in some embodiments comparable to the liver due to seeding with enhanced numbers of regenerative cells. In another embodiment pancreatic islets are created capable of being utilized as a substitute for naturally occurring islets. In other embodiments immune-evasive organs are created utilizing combination of cells which possess ability to evade immunity, thus allowing for tolerance induction without need for immune suppressive activity.

Abstract: Disclosed are systems, means and compositions of matter utilizing artificial intelligence to create unique cells and/or organs from pluripotent stem cells. In one embodiment an artificial intelligence/machine learning approach is utilized to overview and categorize molecular and cellular data regarding normal embryonic development and associated pathways. Through acquiring this information, said artificial intelligence/machine learning system develops a graded list of morphogens/differentiating agents and/or conditions that are utilized to replicate the process of cell/tissue/organ formation artificially. In one embodiment the invention teaches generation of artificial pancreatic organoids through growth factors predicted by said artificial intelligence/machine learning systems. In other embodiments embryogenesis is recapitulated in adult tissue using predicted morphogens and/or extracellular matrix treatments.

Abstract: Disclosed are methods, means and systems of identifying compounds and augment T regulatory cell activity and/or number in vitro and/or in vivo utilizing deep learning approaches. Systems for screening compound libraries in silico are provided as well as laboratory methods of testing modulation of T regulatory cell activity and/or numbers. Results provided by the disclosure will serve as the basis for increasing T regulatory cells, which is desirable in situations of autoimmunity or organ transplantation. In situations of oncology or infectious disease reduction of T regulatory cell number and/or activity is desired.

Abstract: Unique compositions of matter and formulations useful for treatment of COVID-19. Said formulation function by induction of immune modulation, cellular protection, suppression of inflammation and suppression of viral infection. In one embodiment a formulation consists of therapeutic doses of various nutraceuticals include epigallocatechin gallate (EGCG), sulforaphane, and curcumin. In some embodiments, the preparation are utilized as a adjuvant therapeutic, while in other embodiments said formulation is utilized as a monotherapy. Various delivery mechanisms can be used, including oral, transdermal, sublingual, intrarectal and intravenous administration.

Abstract: Disclosed are compositions and methods of treating muscular dystrophies, including Duchenne Muscular Dystrophy (DMD) through administration of fibroblasts and modified fibroblasts systemically and locally. In certain embodiments, fibroblast cells are utilized for replacement of dystrophin through fusion and/or other means of horizontal gene transfer. In other embodiments, the disclosure teaches the use of fibroblasts for reduction of inflammatory reactions and/or immunological reactions which propagate and enhance myodestructive aspects of Duchenne Muscular Dystrophy. In other embodiments, fibroblasts are utilized as vectors for gene therapy and/or gene modifications approaches.

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 one 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 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 one 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: 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: 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.

Abstract: The present disclosure concerns methods and compositions for treating or preventing or reducing the risk of having Amyotrophic Lateral Sclerosis (ALS) in an individual. In particular embodiments, there are methods and compositions related to administering to the individual a therapeutically effective amount of a population of fibroblasts, fibroblast exosomes, IL-2, or a combination thereof.

Abstract: Embodiments of the disclosure include methods and compositions for treatment of lung disease, including at least chronic obstructive pulmonary disease (COPD). In particular cases, fibroblasts (including activated fibroblasts) and/or exosomes thereof are provided to an individual for the treatment of COPD. In particular cases the fibroblasts are activated and/or express one or more particular markers.

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 and therapeutic means for increasing efficacy of immunotherapy such as Tumor Infiltrating Lymphocytes (TILs), Chimeric Antigen Receptor (CAR)-T cells, and other cellular therapies in solid tumors. In one embodiment agents capable of increasing tumor immunogenicity and/or antigen presentation by modulation of tumor stromal cells such as monocytes and pericytes are administered prior to providing immunotherapy in a patient. In some embodiments administration of interleukin-33 together with one or more antioxidants is provided as a means of stimulating expression of HLA and TAP proteins without inducing significant inflammatory response and myeloid derived suppressor cell activation in cancer associated monocytes. In other embodiments the use of histone deacetylase (HDAC) inhibitors together with interferon alpha is disclosed as a means of stimulating the expression of immunogenic molecules on monocytes to increase immunotherapy cell activity.

Abstract: Embodiments of the disclosure include methods and compositions for treatment of lung disease, including at least chronic obstructive pulmonary disease (COPD). In particular cases, fibroblasts (including activated fibroblasts) and/or exosomes thereof are provided to an individual for the treatment of COPD. In particular cases the fibroblasts are activated and/or express one or more particular markers.