A preview of selected articles

Multipotent adult progenitor cells (MAPCs), a plastic-adherent bone marrow-derived population of human multipotent adult stem cells, can undergo long-term culture expansion without significant losses in potency or genomic and epigenetic stability. Furthermore, MAPCs, which are distinct from mesenchymal stem cells, do not evoke an immune response and display potent immunomodulatory/ anti-inflammatory and regenerative properties. The therapeutic potential of MAPC therapy has been supported by the improvements to neurological outcomes observed in preclinical models of hypoxic-ischemic encephalopathy, traumatic brain and spinal cord injury, and stroke, among other conditions. Of particular note, a clinical-grade MAPC product known as MultiStem (Athersys, Inc, Cleveland, Ohio) is currently under evaluation for safety and efficacy in a double-blind, placebo-controlled clinical trial for the treatment of ischemic stroke in human patients. These promising results have driven the further exploration of MAPC therapy as a means to treat brain injuries and improve neurodevelopmental outcomes in preterm neonates, while complementary research has sought to understand the mechanisms by which MAPC therapy improves outcomes. In our first Featured Article published this month in STEM CELLS Translational Medicine, Gussenhoven et al report that systemic MAPC therapy reduces cerebellar injury after asphyxia in fetal sheep in a study that extends previous observations that MAPCs afford cerebral neuroprotection. In a Related Article published recently in STEM CELLS, Yang et al discovered that systemic MAPC therapy enhanced recovery after stroke by altering the expression of immune-related genes and reducing pro-inflammatory signaling in the spleen. Yes-associated protein 1 (YAP1 or YAP) is a transcriptional coactivator of the Hippo pathway that transduces mechanical cues such as extracellular matrix (ECM) rigidity, strain, and shear stress to regulate biological processes that include cell growth and fate decision, organ size control, and regeneration. The activation of the Hippo signaling pathway prompts the phosphorylation and inactivation of YAP1; however, the inhibition of Hippo signaling prevents YAP1 phosphorylation and promotes the relocation of YAP1 from the cytoplasm to the nucleus, where it functions as a transcriptional coactivator for genes associated with cell proliferation, survival, mobility, stemness, and differentiation. Multiple studies have highlighted an important role for YAP1 in controlling the differentiation of various stem and progenitor cell types specifically, activated YAP1 supports the maintenance of the self-renewing state of pluripotent stem cells and the proliferation of tissue-resident stem cells, whereas YAP1 inactivation can promotes efficient stem cell differentiation. Therefore, a deeper understanding of YAP1 function in stem cell biology may permit the enhanced in vitro expansion of stem cells and their efficient differentiation into therapeutically relevant cell types. In our second Featured Article published this month in STEM CELLS Translational Medicine, Yamashita et al demonstrate that the inactivation of YAP1 during the differentiation of human induced pluripotent stem cells (iPSCs) on a laminin-fragment culture substrate significantly improves chondrogenesis and cartilage formation. In a Related Article published recently in STEM CELLS, Xia et al characterized YAP1 as a crucial mechanotransduction signaling mediator that promotes the expansion of inner ear progenitor cells (IEPCs) via the regulation of Wnt/β-catenin activity.