title: Cardiomyogenesis of periodontal ligament-derived stem cells by dynamic tensile strain.
abstract: Cellular therapies for the treatment of myocardial infarction have proven to be an invaluable tool in recent years and provide encouraging evidence for the possibility to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. This study explores the use of a population of stem cells arising from the neural crest and isolated from adult human periodontal ligament along with short-term mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for cellular cardiomyoplasty. Cells were subjected to a short-term dynamic mechanical tension in our custom-built bioreactor and analyzed for cardiomyogenic commitment. Mechanical strain elicited a cardiomyogenic response from the cells following just 2 h of stimulation. Mechanical strain activated and translocated cardiac-specific transcription factors GATA4, MEF2C and Nkx2.5, and induced expression of the sarcomeric actin and cardiac troponin T proteins. Mechanical strain induced production of significantly higher levels of nitric oxide when compared to static controls. Elimination of elevated ROS levels by free radical scavengers completely abolished the cardiomyogenic response of the cells. MicroRNA profile changes in stretched cells were detected for 39 miRNAs with 16 of the differentially expressed miRNAs related to heart development. The use of stem cells in combination with mechanical strain prior to their delivery in vivo may pose a valuable alternative for the treatment of myocardial infarction and merits further exploration for its capacity to augment the already observed beneficial effects of cellular therapies.
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelaez
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA.|Geriatric Research, Education and Clinical Center (GRECC), Miami Veterans Affairs (VA) Medical Center, Miami, FL, USA.
authors.forename: Zenith
authors.initials: Z
authors.lastname: Acosta Torres
authors.affiliation: Geriatric Research, Education and Clinical Center (GRECC), Miami Veterans Affairs (VA) Medical Center, Miami, FL, USA.|Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Tsz Kin
authors.initials: TK
authors.lastname: Ng
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.affiliation: Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA. hcheung@med.miami.edu.|Geriatric Research, Education and Clinical Center (GRECC), Miami Veterans Affairs (VA) Medical Center, Miami, FL, USA. hcheung@med.miami.edu.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Cheung
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D038081:Organogenesis; D010513:Periodontal Ligament / Q000166:cytology*; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D009569:Nitric Oxide
keywords: Cardiomyogenesis; Mechanotransduction; Stem cells; Tensile strain