title: Tissue-specific composite cell aggregates drive periodontium tissue regeneration by reconstructing a regenerative microenvironment.
abstract: Periodontitis is the most common cause of periodontium destruction. Regeneration of damaged tissue is the expected treatment goal. However, the regeneration of a functional periodontal ligament (PDL) insertion remains a difficulty, due to complicated factors. Recently, periodontal ligament stem cells (PDLSCs) and bone marrow-derived mesenchymal stem cells (BMMSCs) have been shown to participate in PDL regeneration, both pathologically and physiologically. Besides, interactions affect the biofunctions of different derived cells during the regenerative process. Therefore, the purpose of this study was to discuss the different derived composite cell aggregate (CA) systems of PDLSCs and BMMSCs (iliac-derived or jaw-derived) for periodontium regeneration under regenerative microenvironment reconstruction. Our results showed although all three mono-MSC CAs were compacted and the cells arranged regularly in them, jaw-derived BMMSC (JBMMSC) CAs secreted more extracellular matrix than the others. Furthermore, PDLSC/JBMMSC compound CAs highly expressed ALP, Col-I, fibronectin, integrin-β1 and periostin, suggesting that their biofunction is more appropriate for periodontal structure regeneration. Inspiringly, PDLSC/JBMMSC compound CAs regenerated more functional PDL-like tissue insertions in both nude mice ectopic and minipig orthotopic transplantation. The results indicated that the different derived CAs of PDLSCs/JBMMSCs provided an appropriate regenerative microenvironment facilitating a more stable and regular regeneration of functional periodontium tissue. This method may provide a possible strategy to solve periodontium defects in periodontitis and powerful experimental evidence for clinical applications in the future. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Implantation, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.|State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.|Research and Development Centre for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Implantation, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.|State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Xicong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Implantation, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.|State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Implantation, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Centre for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.|Research and Development Centre for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010513:Periodontal Ligament / Q000502:physiology*; D012038:Regeneration; D055153:Stem Cell Niche
keywords: cell aggregate; iliac-derived mesenchymal stem cells; jaw-derived mesenchymal stem cells; periodontal ligament-derived stem cells; periodontium regeneration; regenerative microenvironment