You’ve got mail! How often do you send a text, phone a friend, or, if you’re into revivalism, send a pigeon? Our daily lives revolve so heavily around communication; it’s difficult to imagine a world in which we couldn’t express ourselves to others. Not only is this ability crucial in our interpersonal lives, but the enrichment of communication happens within, on a cellular level. Extracellular vesicles (EVs) are vehicles secreted by our cells that contain cargo such as lipids, proteins, and nucleic acids. These vesicles are subsequently taken up by the receiving cells, facilitating a crosstalk that mediates cellular & physiological responses. Researchers in this field are like linguists who not only try to decode this foreign language, but also talk back.
Image from: Chloe Mootz, 2025. Digital painting of two eukaryotic cells participating in EV-mediated cargo transfer using Procreate
There are many different types of EVs. EVs carry specialized cargo, depending on the cell of origin; for example, mesenchymal stem cells and neutrophils. Mesenchymal stem cells can have anti-inflammatory factors within their EVs. On the other hand, neutrophils can leave neutrophil-derived trails as they migrate, like breadcrumbs for other immune cells.
Regenerative therapy is a field in which treatments focus on repairing tissues and cells, often using stem cells that can differentiate into many cell types. These cells can be obtained either from a donor (allogeneic) or from one’s own self (autologous) by harvesting what remains of the adult stem cell population or through induced pluripotent stem cell therapy. Induced pluripotent stem cell therapy involves genetically reprogramming a differentiated or somatic cell to acquire characteristics of an undifferentiated pluripotent stem cell. This then allows them to be differentiated into a specific cell type and then transplanted back into the body. However, for some patients, a therapy that requires harvesting their own cells isn’t feasible. With age, the pool and quality of adult stem cells decline. Furthermore, reprogramming is costly and time-intensive. The way in which cells are delivered can also be invasive, sometimes requiring tissue grafts or intracerebral injections. Moreover, donor cell transplantation requires immunosuppressants and human leukocyte antigen matching. It can increase the risk of graft-versus-host disease and limit scalability.
Image from: Chloe Mootz, 2026. Digital painting of iPSC therapy using Procreate.
Given these issues, how do we combat degenerative diseases in which cells are deteriorating, without using cells? One route is via EVs, which can deliver voicemail-like instructions to diseased cells. Extracellular vesicles do not need to be harvested from the patient themselves, as they can evade the immune system without triggering a response. Furthermore, EVs can cross the blood-brain barrier due to their small size and interactions with epithelial cells. EV’s ability to travel long distances and home in on the specific area in which the message needs to be received makes delivering them minimally invasive. Patients and doctors would be able to access EV products off the shelf, as they can be freeze-dried or stored at 4°C (well above the temperatures required for cells preserved in liquid nitrogen freezers). Not only does this make them accessible to patients in doctors’ offices, but it also offers the potential for a regenerative therapy that can be administered in non-traditional settings, such as field hospitals. Because the contents of EVs depend on the pathophysiological state of the environment, they can also serve as real-time diagnostic biomarkers.
My time pursuing research as a student and learning about regenerative approaches to degenerative diseases has ultimately been guided by firsthand experience with the progression of such debilitating diseases within my family. According to the World Health Organization, over 1 in 3 people are affected by neurological conditions, with some of the leading conditions being stroke, traumatic brain injury (TBI), nerve damage, and dementia. These conditions are characterized by either sudden neuronal death or chronic degeneration. Especially devastating is Alzheimer’s, which is caused by the buildup of misfolded proteins. This protein aggregation blocks synapses and communication, leading to neuronal degeneration. Thus, reducing the formation of the aggregated protein is of great interest.
MicroRNAs (miRNAs) are small molecules that can block protein production. In Alzheimer’s, dysregulation of several miRNAs has been linked to disease. MiRNAs are easily degraded, rendering their therapeutic effect dependent on the rate at which the body clears them. EVs can act as a shuttle system for miRNAs that are downregulated in Alzheimer’s.
Loading of synthetic medicines can be done using methods that temporarily disrupt the EV’s membrane, creating an entry point. The parent cells of EVs can also be genetically engineered via plasmid transfection, a technique for introducing nucleic acids into cells without utilizing a virus. Drugs that may be effective in treating a disease can also be packaged into EVs, improving their retention by protecting them with the lipid membrane and optimizing targeting to the area of interest.
Alternative therapies such as EVs have offered me hope in the fight for time and health of loved ones. Although there is much work to be done in scalability, standardization, and accessibility of regenerative products, they represent an advancement in our understanding of the body and the beginnings of using that knowledge holistically to fight disease. Communication about such treatments not only reignites hope but also generates conversations about how specific improvements can enable therapies to reach the market. Let’s talk about it; it’s what our cells would want!
