Methods of treatment are provided herein, including administration of a population cells modified to enforce expression of an E-selectin and/or an L-selectin ligand, the modified cell population having a cell viability of at least 70% after a treatment to enforce such expression.

The present invention pertains to an inventive release mechanism for extracellular vesicle (EV)-mediated intracellular and intramembrane delivery of therapeutic polypeptides. More specifically, the invention relates to EVs comprising polypeptide constructs which comprise a therapeutic polypeptide releasably attached to an exosomal polypeptide. Furthermore, the present invention pertains to manufacturing methods, pharmaceutical compositions, medical uses and applications, and various other embodiments related to the inventive EVs.

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.

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.

Compositions and methods are provided for reprogramming demal fibroblasts to exhibit neurogenic properties including increased cell expression of NGF and Nt3 in vivo. In accordance with one embodiment such compositions are used in conjunction with standard treatment for use in treating neuropathic pain and stabilizing or stimulating production of PGP9.5+ mature nerve fiber in a diabetic patient’s tissues.

Provided herein are PIWI-interacting RNA (piRNA) derived from therapeutic exosomes, and methods of use thereof to treat a condition requiring tissue repair and/or regeneration. Conditions treated by the exosome-derived piRNAs and/or exosomes carrying the same include, in some embodiments, ischemic injury and/or tissue fibrosis. Also provided are therapeutic compositions comprising exosome-derived piRNA and a pharmaceutically acceptable excipient.

Provided herein are PIWI-interacting RNA (piRNA) derived from therapeutic exosomes, and methods of use thereof to treat a condition requiring tissue repair and/or regeneration. Conditions treated by the exosome-derived piRNAs and/or exosomes carrying the same include, in some embodiments, ischemic injury and/or tissue fibrosis. Also provided are therapeutic compositions comprising exosome-derived piRNA and a pharmaceutically acceptable excipient.

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.

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.

Disclosed are compositions comprising a non-homogenized chorionic matrix, a homogenized amniotic matrix and a homogenized UC (UC) matrix, wherein the non-homogenized chorionic matrix comprises viable cells. Disclosed are methods of making the compositions disclosed herein comprising preparing a non-homogenized chorionic matrix, preparing a homogenized amniotic matrix, preparing a homogenized UC matrix, and combining the non-homogenized chorionic matrix, the non-homogenized chorionic matrix, and the homogenized UC matrix. Disclosed are methods of treating a tissue injury or chronic pain comprising administering any of the disclosed compositions to an area of a subject comprising a tissue injury.