Abstract: Embodiments of the disclosure include means of treating a variety of periodontal and dental diseases using fibroblasts, modified fibroblasts, and derivatives thereof. In one embodiment, the disclosure encompasses the utilization of fibroblasts for treatment of gum disease. In another embodiment, disclosed are means of utilizing fibroblasts and modifications thereof, for preparing gum tissue for placement of an artificial tooth. In another embodiment, fibroblasts are utilized to increase efficacy of bone grafts. In other embodiments, fibroblasts are utilized to generate artificial teeth through utilization of various scaffolding and/or 3 dimensional printing means.

Abstract: Disclosed are means and methods of treating cognitive dysfunction associated with COVID-19 and/or other associated with inflammatory conditions. In one embodiment treatment of COVID-19 cognitive dysfunction performed by administration of nutraceutical means, wherein said nutraceuticals are administered at a frequency and/or concentration sufficient to induce proliferation of endogenous neural progenitor cells and/or protect cells from inflammatory damage. In one embodiment said nutraceuticals are comprised of green tea extract, and/or nigella sativa, and/or pterostilbene, and/or sulforaphane. In some embodiments nutraceutical compositions are utilized to overcome treatment resistant of currently used antidepressants.

Abstract: Described are antigen specific and antigen non-specific means of suppressing development of Type 1 Diabetes in a mammal through administration of exosomes, microvesicles or apoptotic bodies from monocytic lineage cells that have been reprogrammed by contact with mesenchymal stem cells and/or mesenchymal stem cell conditioned media. In one embodiment, the invention provides administration of exosomes that have been generated from monocytic cells that have been loaded with tolerogenic antigens and/or epitopes. In another embodiment the invention provides administration of allogeneic myeloid derived exosomes that are loaded with tolerogenic antigens. In another embodiment the invention provides means of stimulating exosome release in vivo from allogeneic cells that have been administered to the patient in need of treatment.

Abstract: Cell populations and methods of use of mononuclear cells (CMNCs) obtained from dissociated vascular lobules of a perinatal tissue cultured to confluency under hypoxia sufficient to induce translocation of HIF-1 alpha.

Abstract: Disclosed are means, treatments and compositions of matter useful for treatment of chemotherapy/radiotherapy associated cognitive dysfunction. In one embodiment the invention provides the administration of mesenchymal stem cell apoptotic bodies alone or in combination with “regenerative adjuvants” to prevent and/or reverse cognitive dysfunction associated with chemotherapy and/or radiation therapy. In other embodiments the invention teaches the utilization of stem cell apoptotic bodies for induction of neuroregeneration directly or indirectly.

Abstract: Embodiments of the disclosure include methods and compositions for treatment or reduction in risk of coagulopathy of any kind, including associated with inflammation. In specific embodiments, the coagulopathy is associated with upregulated production of tissue factor in the individual. In specific embodiments, the coagulopathy is in an individual that has SARS-CoV-2 infection or is at risk for having SARS-CoV-2 infection. In specific embodiments, the methods and compositions include fibroblasts, and/or modified fibroblasts, and/or derivatives of fibroblasts, including those fibroblasts exposed to TNF-alpha or one or more other inflammatory agents before activation of the fibroblasts.

Abstract: Disclosed are means, methods and compositions of matter useful for quantifying the potency of regenerative therapeutics based on utilization of immunotherapies to induce tissue repair. In one embodiment said immunotherapy with regenerative activity is a T regulatory cell based therapy for stroke whose potency is quantified by assessment of one or more from the following: a) basal production of regenerative factors; b) induced production of regenerative factors; c) ability to prevent apoptosis of a target cell of interest; d) ability to stimulation proliferation of a target cell; and e) ability to induce proliferation of a progenitor cell belonging to tissue type of which therapy is desired.

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 means, methods, and compositions of matter useful for enhancing therapeutic efficacy of fibroblasts, fibroblast products such as exosomes, or fibroblast apoptotic bodies, through modulation of the recipient microbiome prior to, concurrent with, and subsequent to administration of fibroblasts. In one embodiment, assessment of dysbiosis is performed prior to administration of fibroblast therapy, and dysbiosis is repaired by means including: a) microbiome transplant; b) prebiotic treatment; and/or c) probiotic treatment.

Abstract: In some aspects, disclosed herein are methods and compositions for treatment of Parkinson's disease using fibroblasts or cells derived from fibroblasts. Also disclosed herein are methods and compositions for generating dopaminergic cells from fibroblasts. Dopaminergic cells generated from fibroblasts are described. Methods of the present disclosure include methods for treatment or preventing of Parkinson's disease comprising the use of fibroblasts or dopaminergic cells generated from fibroblasts.

Abstract: Disclosed are methods, compositions of matter, and protocols useful for the detection of altered cells in a patient. Immune cells capable of clonal expansion are engineered to produce a soluble signal upon activation and/or clonal expansion. The cells may possess a suicide gene, inducible upon administration pharmacological or light/radiation activatable, so as to eliminate the cells from body when desired. In another embodiment, immune cells produce a localized marker, the marker being visible with imaging technology. In other embodiments cells capable of non-clonal expansion are utilized. The disclosure provides means of utilizing the immunosurveillance properties of immune cells to diagnose and localize diseases associated with alteration of host cells.

Abstract: Disclosed are means of stimulating systemic immunity and reduction of post-surgery tumor metastasis through the concurrent intralymphatic inhibition of NR2F6 and treatment with cannabidiol. In some embodiments NR2F6 is inhibited by high pressure transient delivery of short interfering RNA into tumor draining lymph nodes concurrent with systemic administration of cannabidiol. This combination may be performed together with means that induce immunogenic tumor cell death. Through the combination of immunogenic cell death and immune stimulation, the invention provides a means of enhancing the abscopal effect and in some embodiments to cause immunological mediated destruction primary and secondary neoplasia.

Abstract: The invention provides means, methods, and compositions of matter useful for treatment of viral induced sexual dysfunction. In one embodiment the invention teaches the use of autologous bone marrow mononuclear cells as a source of endothelial repair in penile or clitoral tissues that has been damaged by viral causes. In one embodiment, said viral cause is COVID-19 infection. In some embodiments the invention discloses means of maintaining and/or increasing sexual function, in some cases the invention describes preservation of tissue mass and/or size by administration of regenerative cells. Said cells may be autologous, allogeneic or xenogeneic. In some embodiments the invention teaches the utilization of derivatives of regenerative cells such as exosomes and/or conditioned media.

Abstract: Disclosed are novel method of inducing tissue regeneration through administration of gamma delta T cells that have been endowed regenerative activity. In one embodiment said regenerative active is bestowed upon said cells by culture with a regenerative cell population. In other embodiments a chimeric antigen receptor (CAR) is transfected which induces generation of regenerative substances upon activation of said CAR. Regenerative factors useful for the treatment of the invention depend on the condition for which treatment is desired, for example, in neurological conditions production of brain derived neurotrophic factor is produced upon activation of said CAR, wherein said CAR recognizes antigens or neoantigens associated with neuronal injury.

Abstract: Disclosed are means of enhancing therapeutic effects of fibroblast administration through utilization of extracorporeal shock waves. In one embodiment, enhancement of intravenously administered fibroblast therapeutic activity is accomplished by introducing extracorporeal shock waves to the patient in need of therapy. In one specific embodiment, enhancement of the ability of fibroblasts administered intravenously to treat a condition is accomplished by exposure of areas areas affected by the condition to extracorporeal shock waves. In another specific embodiment, the invention provides transfection of IL-12 and/or IL-23 into fibroblasts to augment regenerative activity, including neuroregenerative and anticancer activity. In further embodiments the invention provides augmentation of regenerative activity by induction of T regulatory cells utilizing IL-35 transfection, wherein said T regulatory cells provide an optimized environment for stimulation of regenerative activity.

Abstract: Disclosed are methods and compositions useful for treatment of blindness or dry macular degeneration. In one embodiment, retinal pigmented epithelial cells are generated from fibroblasts through induction of differentiation, and/or transdifferentiation. In another embodiment, fibroblast-derived products, such as differentiated retinal pigmented epithelial cells, are provided to subjects in a therapeutically effective amount.

Abstract: A method of creating antigen-specific, chimeric antigen receptor (CAR) T cells capable of secreting regenerative growth factors upon activation of said CAR. In one embodiment said regenerative CAR-T cells possess a CAR capable of selectively recognizing damaged tissue. In one embodiment said CAR recognizes damage-associated molecular patterns (DAMPs) such as ATP, HMGB-1, matricryptins, cold-inducible RNA-binding protein, histones and mitochondrial DNA. Upon activation of said CAR said regenerative CAR-T cell is induced to produce one or more regenerative growth factors. In some embodiments the invention provides a suicide gene in said regenerative CAR-T cells in order to remove said cells after their therapeutic purpose is completed.

Abstract: Embodiments of the disclosure include methods of inhibiting and/or reversing blood vessel degeneration in an individual by administering to the individual a therapeutically effective amount of a fibroblast cell population. In specific embodiments, the individual has one or more aneurysms. Also disclosed are methods of inhibiting development of aortic dissection and/or reversing blood flow abnormalities associated with aortic dissection. In specific cases the cells are CD73 -positive and/or CD56-positive.

Abstract: The disclosure encompasses the use of fibroblasts and products derived from fibroblasts for treatment of at least frontotemporal dementia. In particular embodiments, the disclosure teaches administration of cells intravenously, intrathecal or intracerebrally in order to reduce inflammation, enhance neurorgeneration and prevent neuronal dysfunction associated with progranulin abnormalities which characterize frontotemporal dementia. In particular embodiments, the disclosure teaches the utilization of exosomes, or apoptotic bodies derived from fibroblasts. In particular embodiments, the disclosure provides the use of genetically modified fibroblasts in order to augment therapy frontotemporal dementia.

Abstract: Disclosed are compositions of matter, cells, protocols and procedures useful for augmentation of one or more therapeutic activities of fibroblast cellular populations. In one embodiment, fibroblasts are cultured in an acidic pH incubation medium before genetic modification, after genetic modification, or both. In another embodiment, fibroblasts are cultured under hypoxic conditions. In another embodiment, fibroblasts are treated with mitogenic factor-comprising composition(s) to increase the efficacy of genetic modification, wherein the mitogenic factor(s) may be cytokines, peptides, and/or proteins. In another embodiment, a therapeutically effective amount of the genetically modified fibroblasts are provided as a therapeutic application to an individual in need thereof. In another embodiment, the therapeutic application is treatment of fibrosis, treatment of inflammation, acceleration of healing, treatment of clotting disorders, or promotion of angiogenesis.