Abstract: Disclosed are means and compositions of matter for treating degenerative disc disease and associated pain in part by stimulating enhanced local perfusion and reduction of inflammation. In one embodiment administration of inducible pluripotent stem cell derived mesenchymal stem cells is performed wherein said cells are optimized for migration and/or retention into perispinal environment. In some embodiments said mesenchymal stem cells are optimized for enhanced angiogenesis and/or suppression of inflammation. In another embodiment inducible pluripotent stem cell derived T regulatory cells are administered alone or with said mesenchymal stem cells in order to elicit enhanced perispinal perfusion while concurrently reducing inflammation.

Abstract: Methods and compositions of matter for production of pancreatic beta cells, as well as beta-like cells that are capable of producing insulin. Pluripotent stem cells are generated through either viral vector or non-viral vector means and induced into differentiation pathways through environments resembling the pluripotent pancreatic environment. In vivo transfection of dedifferentiation and beta cell differentiation genes are provided in vivo in the pancreatic microenvironment to generate de novo beta cells and islets from differentiated tissue or islet progenitors. Means of inducing differentiation of islet progenitors in vivo are also provided.

Abstract: Compositions of matter and therapeutic means for stimulation bone, cartilage or joint regeneration by pluripotent stem cell derived mesenchymal stem cells alone or in a manipulated manner. “Semidifferentiated” mesenchymal stem cells which possess enhanced ability to generate cartilage, bone, or joint tissue. Gene editing is utilized to generate cells with reduced immunogenicity and enhanced therapeutic potential. Enhancement of therapeutic activity is achieved by transfection of pluripotent stem cells with genes which inhibit apoptosis, thus enhancing lifespan and therapeutic activity of said stem cells. Transfection with antioxidant genes such as superoxide dismutase is utilized to enhance activity of cells when administered in inflammatory environments.

Abstract: Methods and compositions of matter useful for reducing extent of spinal cord injury and/or reversion of spinal cord injury gliosis are disclosed. T regulatory cells can be administered systemically and/or locally to a patient suffering from spinal cord injury. T regulatory cells can be modulated by engineering either through gene modification or culture conditions in order to augment regenerative/antifibrotic properties. Utilizing pluripotent stem cell derived T regulatory cells for spinal cord injury and chimeric antigen receptor T cells.

Abstract: Compositions of matter and treatment protocols for reducing or completely avoiding the need for immune suppression in the context of allograft or xenograft transplantation. Use of mesenchymal stem cells, manipulated mesenchymal stem cells, iPSC derived mesenchymal stem cells, and products of said mesenchymal stem cells for promoting the process of immunological tolerance. In one embodiment the invention provides the use of third party “universal donor” iPSC gene edited mesenchymal stem cells to promote tolerance in context of a solid organ transplant such as renal, cardiac, hepatic or small intestine. In other embodiments endogenous mesenchymal stem cells in composite tissue allografts are activated and/expanded in order to promote tolerogenesis and reduced need for immune suppression.

Abstract: Compositions of matter and means useful for treatment of autoimmunity and/or transplant rejection through generation of T regulatory cells in a manner that recapitulates thymic development. Methods of seeding thymic medullary epithelial cells with pluripotent stem cells such as inducible pluripotent stem cells, followed by exposure to conditions allowing for selective growth and expansion of T regulatory cells. T regulatory cells can be scaled for clinical utilization through the use of three-dimensional adhesive growth matrices as well as addition of FoxP3 inducing cytokines such as interleukin-2.

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: 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 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: Disclosed are novel means of enhancing efficacy of pancreatic islet transplantation through administration of regenerative T cells concurrently with modification of the local microenvironment to provide a tolerogenic and angiogenic milieu. In one embodiment, the liver microenvironment is prepared for receipt of pancreatic islets by administration of tolerogenic cells antigen presenting cells, subsequently followed by administration of T cells and/or T regulatory cells conditioned by regenerative cells, and finally pancreatic islets are administered. In other embodiments devices are provided which allow for concurrent administration of pancreatic islets together with T cells and/or T regulatory cells that have been conditioned with regenerative cells. In another embodiment, the administration of T cells and/or T regulatory cells conditioned by regenerative cells is after administration of therapeutic pancreatic islets.

Abstract: Disclosed are prophylactic and therapeutic approaches to Orthopox viral infections. In one embodiment the invention teaches utilization of regenerative cell conditioned media as a prophylactic/therapeutic agent. Synergies with antivirals and immunotherapies are further described. In one specific embodiment, mesenchymal stem cells are activated in vitro with trigger agents activating Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) and conditioned media is isolated and utilized as a therapeutic. Quantification of activity is performed by assessment of antiviral activity and/or ability to stimulate NK mediated cytolysis. Additionally, means of treating Orthopox viral infections (Smallpox, Monkeypox, etc.) by direct administration of stem cells and/or products thereof such as exosomes are disclosed.

Abstract: Disclosed are means, methods and compositions of matter useful for prevention of space flight associated bone density loss. In one embodiment, the invention provides cellular populations capable of suppressing osteoclast function and/or stimulating osteoblast activity. The use of mesenchymal stem cell populations alone, or more preferably, selected by expression of CD56 protein are disclosed. Cells may be administered systemically, or locally through the use of various matrices disclosed in this invention.

Abstract: Disclosed are means of treatment for age related or premature reproductive failure through concurrent administration of regenerative cells together with adjuvants capable of enhancing activity of said regenerative cells. In one embodiment, the invention provides administration of autologous bone marrow mononuclear cells in the endometrium and ovarian tissue. Administration of said type of regenerative cells is combined with anti-oxidants and/or regenerative adjuvants capable of reducing inflammation and/or fibrosis, as well as providing a suitable environment for optimal regenerative function of stem cells.

Abstract: Disclosed are means, methods and compositions of matter for prevention of hair loss and/or regeneration of hair follicles utilizing stem cell-based approaches and synergies with stimulating and/or hormone modulating agents. In one embodiment the invention discloses specific platelet rich plasma (PRP) combinations alone or with bone marrow stem cells to augment hair restoration and stimulate expansion of hair follicle associated T regulatory cell.

Abstract: Disclosed are methods, means, and compositions of matter useful for enhancing regenerative activity of bone marrow mononuclear cells/aspirate by coadministration with oxytocin. In one embodiment the invention teaches the treatment of peripheral artery disease by intramuscular administration of oxytoxin and bone marrow mononuclear cells/aspirate in proximity. The invention provides therapeutic doses, kits, and adjuvants useful in enhancing regenerative activity of bone marrow mononuclear cells/aspirate.

Abstract: Methods and compositions are provided to treat limb ischemia such as Beurger's Disease through the use of bone marrow stem cells that are administered prior to, concurrently with, and subsequently to administration of agents that modify the microenvironment of the ischemic limb(s). In one embodiment, said agents are antioxidants, more specifically antioxidants capable of diffusing across ischemic areas and preserving regenerative activity of administered stem cells. In another embodiment, the invention provides hormonal modifications to overcome deficiencies associated with ischemia predisposing pathologies.

Abstract: Treatment of rheumatoid arthritis has been revolutionized by the introduction of TNF-alpha blockers, which represent a 40 billion dollar annual market. Unfortunately, a significant proportion of patients fail to respond to these treatments. The current invention provides the use of stem cell conditioned T cells to overcome resistance to TNF-alpha blockers by concurrently providing a source of immune modulatory and regenerative cells that synergize with TNF-alpha blockers.