Implantation of adult human mesenchymal stem cells (MSCs) to treat neural disorders shows promise. Depending on their microenvironment, MSCs could potentially be used for the repair and/or replacement of neurons in traumatic brain injury or the treatment of Parkinsons disease. This cross-disciplinary review incorporates aspects of neuroscience, stem cell biology, cancer biology and immunology to discuss interactions between inflammatory mediators and MSCs. We first discuss the role of microRNAs (miRNAs) in neurological development. Secondly, we discuss the ability of MSCs to transdifferentiate into functional neurons, which are regulated by miRNAs, and the implications of these cells for the therapy of neuropathological states. The administration of effective and safe MSC therapy must acknowledge immune mediators that may predispose the early differentiating MSCs to oncogenic insults. Thus, we discuss a key gene, RE-1 silencing transcription factor (REST), based on its dual role in neurogenesis and cancer development. Immune mediators could be central to MSC responses within a region of tissue injury and are also discussed in detail. Exploring the predisposition of MSCs to oncogenesis is critical for translational science since the implementation of safeguarding measures prior to therapy can lead to the successful delivery of stem cells to patients. The method by which MSCs could be applied for future therapies might require trans-disciplinary approaches for personalized treatments.