title: A hybrid microfluidic system for regulation of neural differentiation in induced pluripotent stem cells.
abstract: Controlling cellular orientation, proliferation, and differentiation is valuable in designing organ replacements and directing tissue regeneration. In the present study, we developed a hybrid microfluidic system to produce a dynamic microenvironment by placing aligned PDMS microgrooves on surface of biodegradable polymers as physical guidance cues for controlling the neural differentiation of human induced pluripotent stem cells (hiPSCs). The neuronal differentiation capacity of cultured hiPSCs in the microfluidic system and other control groups was investigated using quantitative real time PCR (qPCR) and immunocytochemistry. The functionally of differentiated hiPSCs inside hybrid system's scaffolds was also evaluated on the rat hemisected spinal cord in acute phase. Implanted cell's fate was examined using tissue freeze section and the functional recovery was evaluated according to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Our results confirmed the differentiation of hiPSCs to neuronal cells on the microfluidic device where the expression of neuronal-specific genes was significantly higher compared to those cultured on the other systems such as plain tissue culture dishes and scaffolds without fluidic channels. Although survival and integration of implanted hiPSCs did not lead to a significant functional recovery, we believe that combination of fluidic channels with nanofiber scaffolds provides a great microenvironment for neural tissue engineering, and can be used as a powerful tool for in situ monitoring of differentiation potential of various kinds of stem cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1534-1543, 2016.
authors.affiliation: Deparmentof Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hesari
authors.affiliation: Department of Hematology and Blood Banking, Faculty of Medicine, Tarbiat Modaress University, Tehran, Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Deparmentof Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Department of Medical Microbiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
authors.forename: Meysam
authors.initials: M
authors.lastname: Sharifdini
authors.affiliation: Medical Biotechnology and Nanotechnology Department, Faculty of Medicine, Zanjan University of Medical Science, Zanjan, Iran.
authors.forename: Samad
authors.initials: S
authors.lastname: Nadri
authors.affiliation: School of Mechanical and Manufacturing Engineering, Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia.
authors.forename: Majid Ebrahimi
authors.initials: ME
authors.lastname: Warkiani
authors.affiliation: Skin and Stemcell Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehrak
authors.initials: M
authors.lastname: Zare
authors.affiliation: Deparmentof Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D019344:Lactic Acid / Q000737:chemistry; D044085:Microfluidics / Q000379:methods*; D057139:Nanofibers / Q000737:chemistry / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000637:transplantation; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy; D013194:Staining and Labeling; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: human induced pluripotent stem cells (hiPSCs); microfluidics; nanofibers; neural differentiation; tissue engineering