If many stem cell therapies produce their benefits largely through the signaling generated by the transplanted cells, in a brief window of time before these cells die, unable to integrate into the local tissue, then why not skip the cells entirely and just deliver the signals? This is made an easier prospect by the fact that a great deal of cell to cell signaling takes the form of extracellular vesicles such as exosomes, tiny membrane-bound packages of various molecules. Thus researchers don't need to completely map and understand the entire set of signals used in order to recreate most of the signaling effects of stem cells. Given a cultured stem cell population, the exosomes that the cells produce can be harvested and then employed as a therapy. Further down the line, after the mapping and the understanding is complete, then manufacture of exosomes from scratch will probably become the standard approach. For now, cells are required for that much, at least.
The research noted here is an illustrative example of present work on exosome-based regenerative therapies; a fair number of research groups are working towards treatments for various tissue types and age-related conditions. As a class, exosome therapies seem about as promising as early stem cell therapies, based on the results to date in animal models, and are arguably more easily controlled and managed than cells. Just considering the logistics of manufacture and storage, the costs should be significantly lower. Scientists are working their way up from mice to larger animal models, and the first human clinical trials for various conditions are on the near horizon. It is a significant shift in focus for the stem cell research community, and it will be interesting to see where this leads in the next few years.
A team of researchers and ArunA Biomedical, a startup company, have developed a new treatment for stroke that reduces brain damage and accelerates the brain's natural healing tendencies in animal models. The research team created a treatment called AB126 using extracellular vesicles (EV), fluid-filled structures known as exosomes, which are generated from human neural stem cells. Fully able to cloak itself within the bloodstream, this type of regenerative EV therapy appears to be the most promising in overcoming the limitations of many cell therapies - with the ability for exosomes to carry and deliver multiple doses - as well as the ability to store and administer treatment. Small in size, the tiny tubular shape of an exosome allows EV therapy to cross barriers that cells cannot.
Following the administration of AB126, the researchers used MRI scans to measure brain atrophy rates in preclinical, age-matched stroke models, which showed an approximately 35 percent decrease in the size of injury and 50 percent reduction in brain tissue loss - something not observed acutely in previous studies of exosome treatment for stroke. Outside of rodents, the results were replicated using a porcine model of stroke. Based on these pre-clinical results, ArunA Biomedical plans to begin human studies in 2019. The company has plans to expand this initiative beyond stroke for preclinical studies in epilepsy, traumatic brain and spinal cord injuries later this year.
Over 700 drugs have failed in stroke clinical trials, an unprecedented rate thought to be attributed in part to limited and isolated testing often solely in "young" rodent models and focusing on a single secondary injury mechanism. Here, extracellular vesicles (EVs), nanometer-sized cell signaling particles, were tested in a mouse thromboembolic (TE) stroke model. Neural stem cell (NSC) and mesenchymal stem cell (MSC) EVs derived from the same pluripotent stem cell (PSC) line were evaluated for changes in infarct volume as well as sensorimotor function.
NSC EVs improved cellular, tissue, and functional outcomes in middle-aged rodents, whereas MSC EVs were less effective. Acute differences in lesion volume following NSC EV treatment were corroborated by MRI in 18-month-old aged rodents. NSC EV treatment has a positive effect on motor function in the aged rodent as indicated by beam walk, instances of foot faults, and strength evaluated by hanging wire test. Increased time with a novel object also indicated that NSC EVs improved episodic memory formation in the rodent. The therapeutic effect of NSC EVs appears to be mediated by altering the systemic immune response. These data strongly support further preclinical development of a NSC EV-based stroke therapy and warrant their testing in combination with FDA-approved stroke therapies.