title: Periodontal ligament cells cultured under steady-flow environments demonstrate potential for use in heart valve tissue engineering.
abstract: A major drawback of mechanical and prosthetic heart valves is their inability to permit somatic growth. By contrast, tissue-engineered pulmonary valves potentially have the capacity to remodel and integrate with the patient. For this purpose, adult stem cells may be suitable. Previously, human periodontal ligament cells (PDLs) have been explored as a reliable and robust progenitor cell source for cardiac muscle regeneration (Pelaez, D. Electronic Thesis and Dissertation Database, Coral Gables, FL, May 2011). Here, we investigate the potential of PDLs to support the valve lineage, specifically the concomitant differentiation to both endothelial cell (EC) and smooth muscle cell (SMC) types. We were able to successfully promote PDL differentiation to both SMC and EC phenotypes through a combination of stimulatory approaches using biochemical and mechanical flow conditioning (steady shear stress of 1 dyne/cm(2)), with flow-based mechanical conditioning having a predominant effect on PDL differentiation, particularly to ECs; in addition, strong expression of the marker FZD2 and an absence of the marker MLC1F point toward a unique manifestation of smooth muscle by PDLs after undergoing steady-flow mechanical conditioning alone, possible by only the heart valve and pericardium phenotypes. It was also determined that steady flow (which was performed using a physiologically relevant [for heart valves] magnitude of ~5-6 dynes/cm(2)) augmented the synthesis of the extracellular matrix collagen proteins. We conclude that under steady-flow dynamic culture environments, human PDLs can differentiate to heterogeneous cell populations that are relevant to heart valve tissue engineering. Further exploration of human PDLs for this purpose is thus warranted.
authors.affiliation: Tissue Engineering Mechanics, Imaging and Materials Laboratory, Department of Biomedical Engineering, College of Engineering and Computing, Florida International University, Miami, Florida 33174, USA.
authors.forename: Catalina
authors.initials: C
authors.lastname: Martinez
authors.forename: Sasmita
authors.initials: S
authors.lastname: Rath
authors.forename: Stephanie
authors.initials: S
authors.lastname: Van Gulden
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelaez
authors.forename: Abraham
authors.initials: A
authors.lastname: Alfonso
authors.forename: Natasha
authors.initials: N
authors.lastname: Fernandez
authors.forename: Lidia
authors.initials: L
authors.lastname: Kos
authors.forename: Herman
authors.initials: H
authors.lastname: Cheung
authors.forename: Sharan
authors.initials: S
authors.lastname: Ramaswamy
mesh_terms: D061249:Batch Cell Culture Techniques / Q000379:methods; D001705:Bioprosthesis; D019149:Bioreactors; D002454:Cell Differentiation; D002478:Cells, Cultured; D005240:Feasibility Studies; D006350:Heart Valve Prosthesis; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology* / Q000502:physiology*; D012212:Rheology; D023822:Tissue Engineering / Q000379:methods*