Role of mesenchymal stem cells in central nervous system regenerative medicine: past, present, and future

The complex structures that make up the nervous system are susceptible to different types of injury ranging from trauma to chronic diseases that cause progressive deterioration. Consequently, the limited capacity for tissue repair in the central nervous system (CNS) is a tremendous challenge. Although spontaneous neural repair occurs in patients, this process is not robust enough to promote functional and stable recovery of the CNS architecture, demanding external intervention. Over the last 20 years, mesenchymal stem cell (MSC) therapies have been increasingly investigated to treat neurodegenerative disorders, as well as traumatic events such as spinal cord injury (SCI). While earlier studies primarily attributed the effects behind the success of MSC-based therapies to its possible neural differentiation capacity, in the last 10 years it has become evident that most of these beneficial effects are mediated by the secretome of these cells. Indeed, MSCs can secrete potent combinations of bioactive molecules including growth factors, cytokines, lipids, and extracellular vesicles, which in turn play important roles in the modulation of numerous physiological processes within the CNS. Having this in mind the review will discuss how the conceptual use MSCs in CNS regenerative medicine has evolved, as well as their proof of concept on two examples of trauma and neurodegeneration within the CNS: SCI and Parkinson’s disease (PD).