Engineered extracellular vesicles derived from pluripotent stem cells: a cell-free approach to regenerative medicine

The engineered extracellular vesicles (EVs) derived from pluripotent stem cells (PSCs) are a new concept in regenerative medicine. These vesicles are secreted from the embryonic stem cells as well as the induced PSCs (iPSCs) and are involved in the transfer of bioactive molecules required for cell signaling. This review describes the possibilities for their use in the modification of therapeutic approaches in regenerative medicine and targeted therapies. PSCs can differentiate into various cell types that can be useful for tissue engineering or to generate models of diseases in a dish. Compared to cell therapies, engineered EVs are characterized by lower immunogenicity, higher targetability, and improved stability. Some of the applications are angiogenic, tissue restorative, immunomodulatory, and gene therapies for the treatment of certain diseases. iPSC-derived engineered EVs find application in regenerative medicine, drug delivery systems, diagnostics of diseases, and hydrogel systems. In regenerative medicine, they can promote the restoration of cardiac, bone, cartilage, and corneal tissues. Engineered EVs are also employed in drug targeting to particular sites as well as in the diagnosis of diseases based on biomarkers and improving image contrast. Hydrogels that contain EVs provide a depot-based delivery system to slowly release drugs in a controlled manner that enhances tissue repair. Thus, the results described above demonstrate the potential of engineered PSC-EVs for various biomedical applications. Future work will be directed toward expanding the knowledge of engineered PSC-EVs and their possibilities to create new therapeutic approaches based on the functions of these vesicles.