title: Cardiomyogenic Differentiation of Human Dental Follicle-derived Stem Cells by Suberoylanilide Hydroxamic Acid and TheirIn VivoHoming Property.
abstract: The purpose of the present study was to investigate thein vitrocardiomyogenic differentiation potential of human dental follicle-derived stem cells (DFCs) under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the histone deacetylase inhibitor family, and analyze thein vivohoming capacity of induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate adherent growing, expression of MSC markers (CD44, CD90, and CD105), and mesenchymal lineage-specific differentiation potential. Adding SAHA to the culture medium induced the successfulin vitrodifferentiation of DFCs into cardiomyocytes. These iCMs expressed cardiomyogenic markers, including alpha-smooth muscle actin (α-SMA), cardiac muscle troponin T (TNNT2), Desmin, and cardiac muscle alpha actin (ACTC1),at both the mRNA and protein level. For the assessment of homing capacity, PKH26 labeled iCMs were intraperitoneally injected (1×106cells in 100 µL of PBS) into the experimental mice, and the ratios of PKH26 positive cells to the total number of injected cells, in multiple organs were determined. The calculated homing ratios, 14 days after systemic cell transplantation, were 5.6 ± 1.0%, 3.6 ± 1.1%, and 11.6 ± 2.7% in heart, liver, and kidney respectively. There was no difference in the serum levels of interleukin-2 and interleukin-10 at 14 days after transplantation, between the experimental (iCM injected) and control (no injection or PBS injection) groups. These results demonstrate that DFCs can be an excellent source for cardiomyocyte differentiation and regeneration. Moreover, the iCMs can be delivered into heart muscle via systemic administration without eliciting inflammatory or immune response. This can serve as the pilot study for further investigations into thein vitrocardiomyogenic differentiation potential of DFCs under the influence of SAHA and thein vivohoming capacity of the iCMs into the heart muscle, when injected systemically.
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University, Ulsan, Republic of Korea.
authors.forename: Iel-Yong
authors.initials: IY
authors.lastname: Sung
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University, Ulsan, Republic of Korea.
authors.forename: Han-Na
authors.initials: HN
authors.lastname: Son
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Imran
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Bharti
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Ju-Mi
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University, Ulsan, Republic of Korea.
authors.forename: Yeong-Cheol
authors.initials: YC
authors.lastname: Cho
authors.affiliation: Department of Dentistry, Gyeongsang National University School of Medicine and Institute of Health Science, Jinju, Republic of Korea.
authors.forename: June-Ho
authors.initials: JH
authors.lastname: Byun
authors.affiliation: Department of Dentistry, Gyeongsang National University School of Medicine and Institute of Health Science, Jinju, Republic of Korea; Department of Oral and Maxillofacial Surgery, Changwon Gyeongsang National University Hospital, Changwon, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Changwon Gyeongsang National University Hospital, Changwon, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Sung
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Gyeongsang National University School of Medicine and Changwon Gyeongsang National University Hospital, Changwon, Republic of Korea.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Gyu-Jin
authors.initials: GJ
authors.lastname: Rho
authors.affiliation: Department of Dentistry, Gyeongsang National University School of Medicine and Institute of Health Science, Jinju, Republic of Korea; Department of Oral and Maxillofacial Surgery, Changwon Gyeongsang National University Hospital, Changwon, Republic of Korea.
authors.forename: Bong-Wook
authors.initials: BW
authors.lastname: Park
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D017690:Cell Transplantation; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D010865:Pilot Projects; D061251:Primary Cell Culture; D012038:Regeneration; D020107:Troponin T / Q000378:metabolism; D000077337:Vorinostat
chemical_list: C541116:ACTA2 protein, human; C526913:ACTC1 protein, human; D000199:Actins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C545568:TNNT2 protein, human; D020107:Troponin T; D000077337:Vorinostat
keywords: human dental follicle-derived stem cells; suberoylanilide hydroxamic acid