Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel

被引：60

作者：

Chien, Ke-Hung ^{[1
,2
,3
]}

Chang, Yuh-Lih ^{[3
,4
,5
]}

Wang, Mong-Lien ^{[4
,6
]}

Chuang, Jen-Hua ^{[4
,6
]}

Yang, Ya-Chi ^{[4
,6
]}

Tai, Ming-Cheng ^{[1
,2
]}

Wang, Chien-Ying ^{[4
,6
]}

Liu, Yung-Yang ^{[4
,7
,8
]}

Li, Hsin-Yang ^{[6
,9
]}

Chen, Jiang-Torng ^{[1
,2
]}

Kao, Shou-Yen ^{[10
,11
]}

Chen, Hen-Li ^{[10
]}

Lo, Wen-Liang ^{[10
,12
,13
]}

机构：

[1] Triserv Gen Hosp, Dept Ophthalmol, Taipei 114, Taiwan

[2] Natl Def Med Ctr, Taipei 114, Taiwan

[3] Natl Yang Ming Univ, Inst Pharmacol, Taipei 112, Taiwan

[4] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[5] Taipei Vet Gen Hosp, Dept Pharmacol, Taipei 112, Taiwan

[6] Taipei Vet Gen Hosp, Dept Med Res, Taipei 112, Taiwan

[7] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[8] Taipei Vet Gen Hosp, Dept Chest, Taipei 112, Taiwan

[9] Natl Yang Ming Univ, Inst Anat & Cell Biol, Taipei 112, Taiwan

[10] Natl Yang Ming Univ, Inst Oral Biol, Taipei 112, Taiwan

[11] Taipei Vet Gen Hosp, Dept Stomatol, Taipei 112, Taiwan

[12] Taipei Vet Gen Hosp, Dept Stomatol, Div Oral & Maxillofacial Surg, Taipei 112, Taiwan

[13] Natl Yang Ming Univ, Sch Dent, Dept Dent, Taipei 112, Taiwan

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

BONE MORPHOGENETIC PROTEIN-6; HUMAN OSTEOGENIC PROTEIN-1; FERULIC ACID; IPS CELLS; DIFFERENTIATION; CHITOSAN; TISSUE; DELIVERY; REPAIR; CARDIOMYOCYTES;

D O I：

10.1038/s41598-017-18415-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Periodontal disease may cause considerable destruction of alveolar bone, periodontal ligaments (PDLs) and cementum and even lead to progressive oral dysfunction. Periodontal tissue regeneration is the ultimate goal of periodontal disease treatment to reconstruct both structures and functions. However, the regenerative efficiency is low, possibly due to the lack of a proper periodontal microenvironment. In this study, we applied an injectable and thermosensitive chitosan/gelatin/glycerol phosphate hydrogel to provide a 3D environment for transplanted stem cells and to enhance stem cell delivery and engraftment. The iPSCs-BMP-6-hydrogel complex promoted osteogenesis and the differentiation of new connective tissue and PDL formation. In animal models of maxillary-molar defects, the iPSCs-BMP-6-hydrogel-treated group showed significant mineralization with increased bone volume, trabecular number and trabecular thickness. Synergistic effects of iPSCs and BMP-6 increased both bone and cementum formation. IPSCs-BMP-6-hydrogel-treated animals showed new bone synthesis (increased ALP- and TRAP-positive cells), new PDL regeneration (shown through Masson's trichrome staining and a qualification assay), and reduced levels of inflammatory cytokines. These findings suggest that hydrogel-encapsulated iPSCs combined with BMP-6 provide a new strategy to enhance periodontal regeneration. This combination not only promoted stem cell-derived graft engraftment but also minimized the progress of inflammation, which resulted in highly possible periodontal regeneration.

引用

页数：13

共 46 条

[1] Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in vivo [J].