Stem cells are considered as potential therapy for inflammatory disorders, tissue repair, and gene delivery, among others. The heterogeneity of a disease and the underlying disorder of a patient bring up the question on the method by which stem cells should be delivered. This summary discusses potential complex interactions among mediators at sites to tissue insults with stem cells. The chapter selects mesenchymal stem cells (MSCs) as a model, although the discussion is relevant to all stem cells. The review examines how MSCs and their differentiated cells can develop cross communication with soluble factors and cells within the region of tissue damage. Inflammatory cytokines, IL-1, TNFα, and TGFβ are selected to explain how they can affect the responses of MSCs, while predisposing the stem cells to oncogenic event. By understanding the varied functions of MSCs, one will be able to intervene to form a balance in functions, ultimately to achieve safety and efficient application. Cytokines can affect the expression of pluripotent genes such asRESTandOct-4.RESTis a critical gene in the decision of a cell to express or repress neural genes. Since cytokines can affect microRNAs, the review incorporates this family of molecules as mediators of cytokine effects. IFNγ, although an inflammatory mediator, is central to the expression of MHC-II on MSCs. Therefore, it is included to discuss its role in the transplantation of stem cells across allogeneic barrier. In summary, this chapter discusses several potential areas that need to be addressed for safe and efficient delivery of stem cells, and argue for the incorporation of microenvironmental factors in the studies.
