title: The role of RhoA kinase inhibition in human placenta-derived multipotent cells on neural phenotype and cell survival.
abstract: Current advances in stem cell biology have brought much hope for therapy of neuro-degenerative diseases. However, neural stem cells (NSCs) are rare adult stem cells, and the use of non-NSCs requires efficient and high-yielding lineage-specific differentiation prior to transplantation for efficacy. We report on the efficient differentiation of placental-derived multipotent cells (PDMCs) into a neural phenotype with use of Y-27632, a clinically compliant small molecular inhibitor of Rho kinase (ROCK) which is a major mediator of cytoskeleton dynamics. Y-27632 does not induce differentiation of PDMC toward the mesodermal lineages of adipogenesis and osteogenesis, but rather a neural-like morphology, with rapid development of cell extensions and processes within 24 h. Compared with conventional neurogenic differentiation agents, Y-27632 induces a higher percentage of neural-like cells in PDMCs without arresting proliferation or cell cycle dynamics. Y-27632-treated PDMCs express several neural lineage genes at the RNA and protein level, including nestin, MAP2, and GFAP. The effect of the ROCK inhibitor is cell-specific to PDMCs, and is mainly mediated through the ROCK2 isoform and its downstream target, myosin II. Our data suggest that ROCK inhibition and cytoskeletal rearrangement may allow for induction of a neural phenotype in PDMCs without compromising cell survival.
authors: Department of Life Science, Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Chih-Hsiang
authors: CH
authors: Wang
authors: Chia-Ching
authors: CC
authors: Wu
authors: Shan-Hui
authors: SH
authors: Hsu
authors: Jun-Yang
authors: JY
authors: Liou
authors: Yu-Wei
authors: YW
authors: Li
authors: Kenneth K
authors: KK
authors: Wu
authors: Yiu-Kay
authors: YK
authors: Lai
authors: B Linju
authors: BL
authors: Yen
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000577:Amides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D024462:Myosin Type II / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D024462:Myosin Type II