title: Reprogramming of endometrial adult stromal cells in the presence of a ROCK inhibitor, thiazovivin, could obtain more efficient iPSCs.
abstract: Today, there is a need for a platform to efficiently generate and maintain a feeder free culture of pluripotent stem cells by small molecules or pharmacological agents. Induced pluripotent stem cell (iPSC) is considered a promising resource for restorative cell therapy in clinical areas. While fully reprogrammed iPSCs are similar to embryonic stem cells, iPSCs could be derived from the patient's own cells (autologous), which avoids the immune rejection activities. Recent advances have demonstrated that iPSCs could be generated from human fibroblasts using only four transcription factors: OCT4, SOX2, CMYC, and KLF4. However, the limitations of reprogramming technologies include low efficiency, slow kinetics, transgene integration and residual expression. Surprisingly, adult stem cells from human endometrium (endometrial stem cells; EnSCs) express OCT4 and KLF4 pluripotency factors. On the other hand, small molecule inhibitors of specific signaling pathways such as thiazovivin have been used in various aspects of iPSC generation and maintenance. Thiazovivin is a selective small molecule that directly targets Rho-associated kinase (ROCK) and increases expression of pluripotency factors. The process using thiazovivin could be easier, faster and more cost effective than transgene integration into somatic cells. So reprogramming of OCT4 and KLF4 expressing EnSCs by a ROCK inhibitor, thiazovivin, could result in producing more efficient iPSCs compared with fibroblasts or conventional somatic cells without integration any transgene and retroviral vector.
authors.affiliation: Tehran University of Medical Sciences, Applied Cell Sciences Department, Tehran, Iran.
authors.forename: Rashin
authors.initials: R
authors.lastname: Mohseni
authors.forename: Alireza
authors.initials: A
authors.lastname: Shoae-Hassani
authors.forename: Javad
authors.initials: J
authors.lastname: Verdi
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000187:drug effects* / Q000502:physiology; D054337:Cell Dedifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects*; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D011743:Pyrimidines / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects* / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D011743:Pyrimidines; D013844:Thiazoles; C545214:thiazovivin; D054460:rho-Associated Kinases
keywords: Cell differentiation; culture technology; humans; pharmacology; protein signalling modules/scaffolds; stem cells