The disclosure provides means, methods, and compositions of preventing, reducing, and treating kidney failure through the administration of fibroblasts, modified fibroblasts, and/or products derived from fibroblasts. The disclosure may also concern administration of fibroblasts prior to, concurrent with, or subsequent to administration of a nephrotoxic agent results in production of renal function. In some embodiments, fibroblasts are enhanced for augmentation of nephron-regenerative properties through culture under means including hypoxia, histone deacetylase inhibitor treatment, oxytocin, and/or DNA methyltransferase inhibitors.

Embodiments of the disclosure include methods of increasing the efficacy of a fibroblast cell therapy for any medical condition, including degenerative disc disease, by providing at least one anti-inflammatory composition, exosomes and/or apoptotic bodies, stem cells, or a combination thereof; and administering the fibroblast cell therapy. The anti-inflammatory composition may comprise a composition that inhibits and/or reduces TNF-alpha, such as melatonin.

Embodiments of the disclosure include methods of increasing the efficacy of a fibroblast cell therapy for any medical condition, including degenerative disc disease, by providing at least one anti-inflammatory composition, exosomes and/or apoptotic bodies, stem cells, or a combination thereof; and administering the fibroblast cell therapy. The anti-inflammatory composition may comprise a composition that inhibits and/or reduces TNF-alpha, such as melatonin.

Embodiments of the disclosure include methods of increasing the efficacy of a fibroblast cell therapy for any medical condition, including degenerative disc disease, by providing at least one anti-inflammatory composition, exosomes and/or apoptotic bodies, stem cells, or a combination thereof; and administering the fibroblast cell therapy. The anti-inflammatory composition may comprise a composition that inhibits and/or reduces TNF-alpha, such as melatonin.

Embodiments of the disclosure concern methods and compositions related to cancer treatment for an individual utilizing recombinant fibroblast cells that comprise one or more activities that are endothelial cell-like. The cells are delivered to a tumor microenvironment following which their death results in destabilization of the tumor vasculature. In particular embodiments, the fibroblast cells recombinantly express one or more of ETV2, FOXC2, and FLI1.

Embodiments of the disclosure concern methods and compositions related to cancer treatment for an individual utilizing recombinant fibroblast cells that comprise one or more activities that are endothelial cell-like. The cells are delivered to a tumor microenvironment following which their death results in destabilization of the tumor vasculature. In particular embodiments, the fibroblast cells recombinantly express one or more of ETV2, FOXC2, and FLI1.

The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.

The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

In some aspects, disclosed herein are methods and compositions for treatment or prevention of cerebral palsy using fibroblasts or derivatives thereof. Disclosed herein are fibroblasts and derivatives thereof capable of inducing neurogenesis and/or reducing inflammation in a subject. In some cases, the disclosed methods comprise use of conditioned fibroblasts. Fibroblasts may be conditioned with agents capable of enhancing therapeutic efficacy, for example oxytocin and/or human chorionic gonadotrophin (hCG).