One approach to regenerative medicine is to use donor extracellular matrix as a scaffolding material. The extracellular matrix is the support structure created by cells that determines the structural properties of a tissue. Its presence in a regenerative therapy can guide cells to rebuild lost tissue to some degree, but a better understanding of how this actually works under the hood could be used to improve the quality of the outcome, as well as to hopefully allow the development of a viable artificial replacement for natural donor matrix materials.
Researchers have identified a mechanism by which bioscaffolds used in regenerative medicine influence cellular behavior, a question that has remained unanswered since the technology was first developed several decades ago. Bioscaffolds composed of extracellular matrix (ECM) derived from pig tissue promote tissue repair and reconstruction. Currently, these bioscaffolds are used to treat a wide variety of illnesses such hernias and esophageal cancer, as well as to regrow muscle tissue lost in battlefield wounds and other serious injuries.
Researchers know that ECM is able to instruct the human body to replace injured or missing tissue, but exactly how the ECM material influences cells to cause functional tissue regrowth has remained a fundamental unanswered question in the field of regenerative medicine. In the new study, the team showed that cellular communication occurs using nanovesicles, extremely tiny fluid-filled sacs that bud off from a cell's outer surface and allow cells to communicate by transferring proteins, DNA and other "cargo" from one cell to another. Exosomes are present in biological fluids such as blood, saliva and urine, where they influence a variety of cellular behaviors, but researchers had yet to identify them in solid body tissues. "We always thought exosomes are free floating, but recently wondered if they are also present in the solid ECM and might facilitate the cellular communication that is critical to regenerative processes."
To explore this possibility, researchers used specialized proteins to break up the ECM, similar to the process that occurs when a bioscaffold becomes incorporated into the recipient's tissue. The research team then exposed two different cell types - immune cells and neuronal stem cells - to isolated matrix bound vesicles, finding that they caused both cell types to mimic their normal regrowth behaviors. "Sure enough, we found that vesicles are embedded within the ECM. In fact, these bioscaffolds are loaded with these vesicles. This study showed us that the matrix bound vesicles are clearly active, can influence cellular behavior and are possibly the primary mechanism by which bioscaffolds cause tissue regrowth in the body."