A Preview of Select Articles

The transplantation/administration of cells differentiated from human pluripotent stem cells (hPSCs), including embryonic stem cells and patient-specific induced pluripotent stem cells (iPSCs), represents a promising therapeutic strategy for a wide range of conditions. However, there exists the possibility that the differentiated progeny of hPSCs may accumulate proliferation-enhancing abnormalities during in vitro culture or that hPSCs may “survive” the differentiation process and contaminate the final cell product, with both these scenarios representing a tumorigenic threat. Proposed solutions to this problem have included the screening and identification of “safe” hPSC clones or the optimized differentiation of hPSCs into the somatic cell type required; however, such “indirect” strategies fail to negate the risk of tumorigenicity. Therefore, we require a combination of pretransplant safety assessments with a means to track, target, and eliminate potentially problematic cells for hPSC-based regenerative therapies to safely advance. How far have we come toward achieving this goal? In our first Featured Article published in STEM CELLS TRANSLATIONAL MEDICINE this month, Tanimoto et al exploit the inherent characteristics of human iPSC-derived neural stem/progenitor cells (hiPSC-NS/PCs) to monitor undifferentiated and potentially tumorigenic cells post-transplantation in a noninvasive manner in an attempt to ensure the safe development of this treatment strategy. In a Related Article published in STEM CELLS, Ide et al described a novel method for the efficient generation of a diverse selection of tumorigenic cell-targeting lentiviral vectors that can specifically and efficiently eliminate undifferentiated hPSCs both in vitro and in vivo. Ongoing neurogenesis in the adult mammalian brain occurs primarily via the activity of NS/PCs residing in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus. Studies have provided evidence for the upregulation of adult neurogenesis in response to various pathological conditions to promote functional recovery of the damaged brain. The potentiation of this limited regenerative response represents a promising means to remedy a variety of conditions that impact the central nervous system, and while the infusion of growth factors can boost the neurogenesis of NS/PCs, prolonged exposure can negatively impact their differentiation. Such unwanted side effects have prompted the exploration of the paracrineacting proregenerative capacity of mesenchymal stem cells (MSCs) as an alternative. Exosomes represent one MSC-derived paracrineacting factor that may positively influence adult neurogenesis through the transport of proteins, lipids, and nucleic acids. Can we now improve the regenerative potential of MSC exosomes and construct a stem cell-free therapeutic approach to promote functional recovery in the damaged brain? In our second Featured Article published in STEM CELLS TRANSLATIONAL MEDICINE this month, Chen et al describe how prostaglandin E2 receptor 4 (EP4) antagonist-induced MSCs secrete exosomes containing a myelin-associated enzyme with the ability to promote neurogenesis in the damaged hippocampi. In a Related Article published in STEM CELLS, Cameron et al established that neural stem cells (NSCs) resist apoptosis and ensure ongoing neurogenesis following exposure to concurrent chemotherapy and radiotherapy, thereby suggesting the relative safety of targeting neurogenic brain regions during the treatment of glioblastoma.