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: Disclosed herein are methods and compositions for treatment and prevention of alopecia, including alopecia areata. Aspects are directed to methods for stimulating or accelerating hair follicle regeneration. Certain aspects are directed to methods for treating alopecia areata comprising administration of fibroblasts and/or a fibroblast derived product to a subject suffering from alopecia areata. In some cases, a fibroblast derived product is conditioned media, exosomes, or apoptotic bodies from fibroblasts, formulated for topical use for treatment or prevention of alopecia areata.

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: The present disclosure provides methods, compositions, and systems for producing and using organoids comprising fibroblasts. The organoids can be generated and placed in a particular storage matrix which allows for sufficient conditions for transport and reduces damage to cells in the organoids compared to known media. The organoids may be utilized for extended release of the fibroblasts for cell therapy and also for drug delivery at a target site following administration to an individual in need thereof.

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: 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: 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: Embodiments of the invention concern the regeneration of chondrocytes and cartilage-type cells. In certain embodiments, one or more genes are employed for the regeneration of chondrocytes and cartilage-type cells. In particular embodiments, one or more gene therapy regimens are employed for the regeneration of chondrocytes and cartilage-type cells. In particular aspects, embodiments concern cartilage repair, such as articular cartilage repair. More particularly, embodiments for the disclosure concern using gene therapy for the attraction, generation and/or regeneration of chondrocytes or other cartilage-type cells and/or the generation and/or repair of cartilage tissue. In specific embodiments of the disclosure, gene therapy is provided that is capable of attracting and/or generating desired cells in vivo.

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: 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: 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: 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: 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.

Abstract: Disclosed are treatments, compositions of matter, and protocols for reducing, ameliorating, or reversing excess inflammation and/or cytokine storm through administration of Sphagnum and/or extracts thereof. In particular embodiments, a patient at risk for cytokine storm is administered a Sphagnum extract at a concentration sufficient to induce an immunomodulatory change in said patient, including suppression of macrophage activation, reduction of neutrophil activation and inhibition of DNA extracellular trap release. In some embodiments, Sphagnum, or extracts thereof are administered together with other agents to enhance activity in treatment of Covid-19 infection and associated pathologies. In some embodiments, humic acid and/or analogues thereof are administered for reduction of pathological inflammation and/or stimulation of immunity.

Abstract: Embodiments of the disclosure include methods and compositions related to prevention of spontaneous miscarriage in an individual. In certain cases, fibroblasts are provided in an effective amount to an individual in need thereof. Alternatively or in addition, lymphocytes are obtained, cultured with fibroblasts, and provided to an individual. Fibroblasts may modulate an immune response in an individual, thereby reducing the risk of spontaneous miscarriage.

Abstract: Disclosed are means of enhancing therapeutic activities of fibroblasts through manipulation of nuclear receptor activation accomplished by, intra alia, alteration in hormone levels. In some embodiments angiogenic, and/or neurogenic, and/or immunomodulatory activities of fibroblasts are increased by normalization or augmentation of sex-specific hormones. In one embodiment a candidate for fibroblast therapy is administered hormones, pro-hormones, or growth factors to augment therapeutic activities of fibroblasts. In some embodiments fibroblasts are treated in vitro prior to administration with various hormones and/or growth factors in order to augment therapeutic activities of said cells.

Abstract: Disclosed are means, methods and compositions of matter for treatment of Graves’ Disease using non-modified and/or modified fibroblasts for promotion of immunological tolerance, and/or stimulation of antigen-specific tolerance. In some embodiments, fibroblasts are administered together with antigens associated with Graves’ Disease such as the thyrotropin receptor protein and/or peptides and/or altered peptide ligands derived thereof. In some embodiments, co-administration refers to administration simultaneously or within temporal proximity of each other. In some embodiments, co-administration refers to loading of fibroblasts with antigens and/ or epitopes of antigens associated with Graves’ Disease.

Abstract: Embodiments of the disclosure encompass methods and compositions related to treatment of Acute Respiratory Distress Syndrome caused by any reason, including caused by a coronavirus, for example. In particular embodiments, fibroblasts are delivered to an individual in need thereof to stimulate generation of T regulatory cells that may or may not be FoxP3-positive, and/or immune regulatory cells previously exposed to fibroblasts are delivered to the individual.

Abstract: Embodiments of the disclosure concern methods and compositions of treating or preventing viral infection, including of SARS-CoV-2, for example. In specific embodiments, one or more adjuvants are delivered to an individual receiving and/or having received fibroblasts and/or fibroblast-derived exosomes. In specific cases, the adjuvants comprise particular peptides, chloroquine and/or hydroxychloroquine, and/or one or more activators of one or more toll like receptors.