MicroRNA-132 directs human periodontal ligament-derived neural crest stem cell neural differentiation.

Neurogenesis is the basis of stem cell tissue engineering and regenerative medicine for central nervous system (CNS) disorders. We have established differentiation protocols to direct human periodontal ligament-derived stem cells (PDLSCs) into neuronal lineage, and we recently isolated the neural crest subpopulation from PDLSCs, which are pluripotent in nature. Here, we report the neural differentiation potential of these periodontal ligament-derived neural crest stem cells (NCSCs) as well as its microRNA (miRNA) regulatory mechanism and function in NCSC neural differentiation. NCSCs, treated with basic fibroblast growth factor and epidermal growth factor-based differentiation medium for 24 days, expressed neuronal and glial markers (ßIII-tubulin, neurofilament, NeuN, neuron-specific enolase, GFAP, and S100) and exhibited glutamate-induced calcium responses. The global miRNA expression profiling identified 60 upregulated and 19 downregulated human miRNAs after neural differentiation, and the gene ontology analysis of the miRNA target genes confirmed the neuronal differentiation-related biological functions. In addition, overexpression of miR-132 in NCSCs promoted the expression of neuronal markers and downregulated ZEB2 protein expression. Our results suggested that the pluripotent NCSCs from human periodontal ligament can be directed into neural lineage, which demonstrate its potential in tissue engineering and regenerative medicine for CNS disorders.

Concise Review: The Deleterious Effects of Cigarette Smoking and Nicotine Usage and Mesenchymal Stem Cell Function and Implications for Cell-Based Therapies.

Stem cell sources for cell-based therapeutics are often screened for infectious agents and genetic diseases prior to implantation; however, there are other risk factors that are often overlooked, which may ultimately lead to less efficacious clinical outcomes. One such risk factor is exposure of mesenchymal stem cells (MSCs) to cigarette smoke or nicotine. Recent data have shown that exposure to cigarette smoke or nicotine leads to decreased regenerative potential, namely decreased proliferation, decreased migration, and decreased differentiation potential of exposed MSCs. This review provides a brief introduction into MSCs and their respective niches and a summary regarding the interactions of cigarettes and nicotine with MSCs populations. Specifically, the effects of cigarette smoke and nicotine on the regenerative potential of MSCs (i.e., proliferation, migration, and differentiation) will be covered with an emphasis on considerations for the development of future cell-based clinical trials and therapies. Stem Cells Translational Medicine 2017;6:1815-1821.

Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential.

Adult stem cells are critical for the healing process in regenerative medicine. However, cigarette smoking inhibits stem cell recruitment to tissues and delays the wound-healing process. This study investigated the effect of nicotine, a major constituent in the cigarette smoke, on the regenerative potentials of human mesenchymal stem cells (MSC) and periodontal ligament-derived stem cells (PDLSC). The cell proliferation of 1.0 µM nicotine-treated MSC and PDLSC was significantly reduced when compared to the untreated control. Moreover, nicotine also retarded the locomotion of these adult stem cells. Furthermore, their osteogenic differentiation capabilities were reduced in the presence of nicotine as evidenced by gene expression (RUNX2, ALPL, BGLAP, COL1A1, and COL1A2), calcium deposition, and alkaline phosphatase activity analyses. In addition, the microRNA (miRNA) profile of nicotine-treated PDLSC was altered; suggesting miRNAs might play an important role in the nicotine effects on stem cells. This study provided the possible mechanistic explanations on stem cell-associated healing delay in cigarette smoking.