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 methods, and compositions useful for stimulation of immunity towards cancer by utilizing dendritic cells and products therefrom that have been stimulated and/or incorporated mRNA encoding survivin and/or related gene sequences, defined herein as “survivin modified mRNA”. In one embodiment dendritic cells generated from allogeneic “off the shelf” sources are transfected with survivin modified mRNA and the cells are administered in an immunogenic manner. In some embodiments transfected dendritic cells are induced to undergo immunogenic cell death ex vivo subsequently to which they are used as immunogenic stimuli. In other embodiments preparation of the injection site is performed prior to administration of dendritic cells that have been transfected with survivin modified mRNA by pre-administration of agents increasing the number of local dendritic cells in the skin.

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: Described are means, methods, and compositions useful for treatment of multiple sclerosis through the utilization of fibroblasts and/or derivatives thereof to concurrently stimulate regenerative processes while inducing a protolerogenic immune modulatory program. In certain embodiments, fibroblasts are selected for the concurrent properties of immune modulation and regeneration by enrichment for CD73 expressing fibroblasts. In particular embodiments, stimulation of regeneration implies activation of endogenous neural progenitor cells. In some embodiments, stimulation of regeneration implies induction of remyelination. The utilization of fibroblasts as a superior source for immune modulation, prevention of immune mediated pathology, and activation of T regulatory cells is provided within the context of multiple sclerosis.

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.

Abstract: Disclosed herein are methods and compositions for reducing inflammation in a subject. Aspects are directed to reduction of pulmonary inflammation using fibroblasts or fibroblast derived products. In some cases, fibroblasts or fibroblast-derived products are provided to a subject to reduce pulmonary inflammation, thereby treating or preventing airway allergy, asthma, or asthma-related symptoms. Embodiments encompass use of fibroblast-derived products, including exosomes, conditioned media, and other components derived from fibroblasts.

Abstract: The invention provides means, methods and some compositions of matter useful to treat ovarian failure. In one embodiment progenitor cells possessing ability to differentiate along the monocytic and granulocyte linages are utilized as a source of cytokines for stimulation of ovarian repair/regeneration. Generation of said cells, such as classically termed myeloid derived suppressor cells is performed from sources including cord blood, bone marrow, mobilized peripheral blood and pluripotent stem cells. The invention further provides means of suppressing fibrosis and ongoing inflammation associated with ovarian dysfunction.

Abstract: Embodiments of the disclosure include methods and compositions for disc repair in a mammal using conditioned media (and/or one or more components therefrom) from fibroblasts that have been de-differentiated and cultured optionally with one or more particular conditions and/or compositions. In specific cases, fibroblasts that have been de-differentiated are exposed to hypoxia, histone deacetylase inhibitor(s), DNA methyltransferase inhibitor(s), or a combination thereof, and the conditioned media therefrom is provided in an effective amount to an individual.

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: Disclosed are novel cellular compositions of matter and treatment means for generation of universal donor regenerative T cells by exposure to mesenchymal stem cells or supernatant derived thereof. In one embodiment, regenerative T cells are created by differentiation of pluripotent stem cells in the presence of supernatant generated from activated mesenchymal stem cell population. The invention provides for creation of T cells which are capable of endowing regenerative activity, and/or anti-inflammatory, and/or angiogenic activity.

Abstract: Disclosed are means, methods and compositions of matter useful for generation of conditioned media from endothelial progenitor cells (EPC). In one embodiment, EPC are extracted, dedifferentiated into inducible pluripotent stem cells (iPSC) and said iPSC are differentiated into the EPC lineage. The differentiated EPC are utilized as producers of conditioned media for therapeutic purposes. In one embodiment EPC are subjected to one or more stressors, after which conditioned media is extracted and in some cases concentrated. Said conditioned media can be utilized as a therapeutic agent or can be used in the generation of immune modulatory cells.

Abstract: Disclosed are means, methods and compositions of matter useful for generation of conditioned media from mesenchymal stem cells (MSC). In one embodiment MSC are extracted, dedifferentiated into inducible pluripotent stem cells (iPSC) and said iPSC are differentiated into the MSC lineage. The differentiated MSC are utilized as producers of conditioned media for therapeutic purposes. In one embodiment MSC are subjected to one or more stressors, after which conditioned media is extracted and in some cases concentrated. Said conditioned media can be utilized as a therapeutic agent or can be used in the generation of immune modulatory cells.

Abstract: Disclosed are methods, compositions of matter and protocols useful for restoring/enhancing endometrial function by use of gene therapy. In one embodiment genes associated with endometrial preservation and/or regeneration are inserted into the endometrium and/or accessory tissues. Suppression of fibrosis, inflammation and stimulation of regeneration is accomplished by the practice of the current invention.

Abstract: Disclosed are methods, compositions of matter and protocols useful for restoring/enhancing endometrial function by administration of regenerative cells. In one embodiment cells capable of decreasing fibrosis, stimulation of angiogenesis, and augmenting hormone responsiveness are administered systemically or locally. In some embodiments cells utilized are autologous or allogeneic mesenchymal stem cells.

Abstract: Disclosed are compositions of matter, protocols, and procedures useful for generation of mesenchymal stem cells capable of withstanding the microenvironment of degenerating ovaries. In one embodiment mesenchymal stem cells are pre-treated under conditions capable of upregulating cytoprotective responses and genes, such as HIF-1 alpha and hemoxygenase. In other embodiments mesenchymal stem cells are temporarily pulsed with hypoxia and/or acidity in order to prime them for the harsh environment of degenerating ovarian tissue. Through this approach increased viability of mesenchymal stem cell subsequent to intra-ovarian administration is achieved.

Abstract: Disclosed are novel means of generating cells uniquely suited for treatment of ovarian failure. In one embodiment regenerative cells are pretreated with growth factor-comprising composition(s), wherein the growth factor(s) may be cytokines, peptides, and/or proteins. In another embodiment regenerative cells are cultured with primed plasma extracts. In another embodiment, regenerative cells are cultured under hypoxic conditions together with cytokines prior to administration to an individual. Regenerative cells useful for the current invention including mesenchymal and hematopoietic stem cells, as well as various growth factor producing cells.

Abstract: Disclosed are means and methods useful in selecting osteoarthritis patients most likely to respond to regenerative medicine therapy. One means of practicing the invention is to determine quantity and quality of inflammatory exosomes generated from the tissue adjacent to the injured cartilage. In another embodiment the invention provides detection of exosomes produced by inflammatory processes local or systemic to the body. In some embodiments therapies are tailored to the extent of inflammatory exosomes.

Abstract: Disclosed are methods, protocols and compositions of matter using for treatment of ovarian failure through administration of cells expressing FoxP3 as a monotherapy or as a facilitator to enhance therapeutic efficacy of cells and/or cytokines. In one embodiment FoxP3 expressing cells are concentrated from allogeneic umbilical cord blood, activated ex vivo with anti-CD3 and anti-CD28 antibodies and administered into the ovary alone or with regenerative cells such as stem cells. In one embodiment stem cells administered are of the CD105 expressing lineage.

Abstract: Described are protocols, compositions of matter and therapeutic means useful for treatment of ovarian failure caused by oncology treatments. The utilization of natural killer cells allows for dual activity of tissue regeneration in the ovary, while concurrently inhibiting possibility of oncology relapse. In embodiments NK cells are injected as an adjuvant to stem cell and/or regenerative cell therapy to not only enhance therapeutic effect but also to reduce probability of tumor relapse.