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: 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: 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 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: Disclosed are compositions of matter, protocols and procedures useful for preventing/treatment ovarian failure. In one embodiment cytokines promoting anti-inflammatory/regenerative activity are administered systemically, or locally in order to preventing ovarian degeneration/fibrosis. In one embodiment low dose interleukin-2 is administered either alone or with adjuvant cytokines to induce an increase in FoxP3 expressing CD4 cells. In some embodiments in vivo generation of FoxP3 expressing CD4 cells is associated with stimulation of intra-ovarian angiogenesis and prevention of fibrosis.

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: 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.

Abstract: Disclosed are methods, protocols and compositions of matter useful for the treatment of menopause associated reduction in bone density or osteoporosis. In one embodiment patients with increasing follicle stimulating hormone are administered regenerative cells into the ovarian follicle. Regenerative cells may be from autologous, allogeneic or xenogeneic sources. In some embodiments regenerative cells are from bone marrow, placental, umbilical cord, cord blood, menstrual blood or peripheral blood origin.

Abstract: Disclosed are means of assessing the likelihood of a patient to respond positively to stem cell therapy for cartilage regeneration. In one embodiment enhanced inflammatory cytokines are reduced anti-inflammatory cytokines are assessed in the plasma of a potential patient to assess likelihood of response to therapy. In other embodiments intra-articular or synovial fluid is assessed for levels of cytokines that are detrimental to the success of the stem cell therapy. In other embodiments quality of stem cells in the patient are assessed for cytokine to determine suitability for use in stem cell therapy.

Abstract: Disclosed herein, in certain embodiments, are methods and compositions for treatment of acute respiratory distress syndrome (ARDS) induced by, inter alia, viral agents, comprising administration of fibroblasts, and/or fibroblast derivatives, and/or fibroblast apoptotic bodies. In one embodiment, a patient infected with coronavirus (COVID19) ARDS is administered a concentration of fibroblasts, intravenously, ranging from 10,000 fibroblasts to 300 million fibroblasts, based on patient characteristics and cause of ARDS. In some embodiments, fibroblasts are administered in a non-activated form, whereas in other embodiments, fibroblasts are treated under conditions stimulating enhanced activities beneficial to treatment of ARDS.

Abstract: Increasing therapeutic activity of fibroblasts through suppression of complement activation is disclosed. Embodiments of the disclosure teach that viability of fibroblasts in blood and/or in vivo is increased by inhibition of complement activation. In another embodiment, the blockade of complement is utilized to enhance ability of fibroblasts to suppress inflammation, stimulate generation of T regulatory cell, and inhibit pathologic T cell responses. Other enhancements of fibroblast activity disclosed as a results of complement activation include stimulation of cytokine production, release of antimicrobial and/or antiviral proteins, as well as enhancement of regenerative activities.

Abstract: Disclosed are means, methods, and compositions of matter useful for treatment of neuroinflammation, autoimmunity, transplant rejection, or graft versus host disease (GVHD) comprising exposing autologous immune cells to allogeneic amniotic fluid derived stem cells. In one embodiment peripheral blood mononuclear cells are cultured in the presence of amniotic fluid stem cells in the presence of interleukin-2 for a period of time sufficient to endow tolerogenic properties. Said tolerogenic properties include ability to suppress adaptive or innate immune responses. In another embodiment the invention provides methods of generating antigen specific immune regulatory cells by culture of lymphocytes together with amniotic fluid stem cells in the presence of antigen to which specific immune regulation is desired.

Abstract: Disclosed are means of augmenting efficacy of stem cell therapy for articular tissues through introduction of a step to reduce oxidative stress inside the joint before administration of stem cells. In one embodiment reduction of oxidative stress and/or inflammation is accomplished by administration of anti-oxidant agents locally in the tissue in which stem cell administration is anticipated to. In one embodiment administration of hydrogen gas is provided as a “preconditioning” step before administration of stem cell therapy. In one embodiment cell therapy is a same day non manipulated procedure involving administration of bone marrow aspirate.

Abstract: Methods of enhancing efficacy of cartilage regenerative therapies through reducing particulate and/or cellular debris residing in the intra-articular space. In one embodiment the invention teaches administration of low-dose protease and/or matrix metalloprotease and/or hyaluronidase prior to administration of stem cells in order to clear tissue of debris capable of suppressing regenerative activity of stem cells. In one embodiment of the invention clinical grade hyaluronidase is administered intra-articular in a patient receiving bone marrow aspirate/mononuclear cell therapy.

Abstract: Disclosed are therapeutic means of suppressing degeneration of cartilage in conditions such as arthritis or other degenerative pathologies through administration of myeloid derived suppressor cells or exosomes produced by said cells. In one embodiment myeloid derived suppressor cells are generated by intravenous administration of a mobilizing cytokines followed by collection of myeloid derived suppressor cells through an apheresis means, followed by subsequent introduction into the intra-articular space. In other embodiments allogeneic myeloid derived suppressor cells are administered from an allogeneic source such as umbilical cord blood mononuclear cells.