Paracrine signaling is a form of cell-to-cell communication that has been observed to be responsible for the regenerative power of many cell-based therapies such as mesenchymal stromal cells (MSCs). To harness this unique feature, many researchers have ventured into the world of extracellular vesicles (EVs) and exosomes to create safer and potentially more potent cell-free approaches to treat various diseases. One such researcher is Dr. Ashok Shetty, a neuroscientist and professor at the department of molecular and cellular medicine and associate director for the Institute for Regenerative Medicine at Texas A&M University.
Dr. Shetty has dedicated his life to neuroscience – he has been studying the effects of both human MSCs and human induced pluripotent stem cell (hiPSC) derived neural stem cells (NSCs) on neuroregeneration, neuroprotection and neural plasticity. In this delightful and enlightening interview, Dr. Shetty discusses key findings from intranasal administration of EVs from human bone marrow derived MSCs in the forebrain of mice  – see this recent publication. In this study, Dr. Shetty’s group was not only able to demonstrate the effectiveness of intranasal administration of EVs but they were also able to show distribution and tendencies of various neural cell types to pick up EVs. Dr. Shetty has also studied and compared differences between MSC and NSC in traumatic brain injury (TBI) models, data yet to be published.
One of the biggest challenges in EV therapeutics is in assessing appropriate doses, Dr. Shetty shares his strategies and experiences in neuro diseases and how or why intranasal administration might be advantageous from various perspectives. Without fail, we also discussed how all of this would be relevant to COVID including the challenges in COVID treatments such as intervention strategies.
All truths are easy to understand once they are discovered; the point is to discover them.
– Galileo Galilei
In closing, we discover how Dr. Shetty’s career began, from his fascination in neuro anatomy, to his path into academia and continued research that has evolved over time. This interview, to say the very least, has sparked my interest in neuroregeneration and possible mechanisms that MSC and MSC-EVs would play. He has left me with many things to ponder upon, certainly the right questions to ask as I end this with Dr. Shetty’s favorite quote from Galileo “All truths are easy to understand once they are discovered; the point is to discover them”.
 Kodali et. al. Intranasally administrated human MSC-derived extracellular vesicles pervasively incorporate into neurons and microglia in both intact and status epilepticus injured forebrain. Int. J. Mol. Sci. 2020, 21(1), 181.