Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion

被引：117

作者：

Gorin, Caroline ^{[1
,2
,3
]}

Rochefort, Gael Y. ^{[1
,2
]}

Bascetin, Rumeyza ^{[4
,5
,6
]}

Ying, Hanru ^{[4
,5
,6
]}

Lesieur, Julie ^{[1
,2
]}

Sadoine, Jeremy ^{[1
,2
]}

Beckouche, Nathan ^{[4
,5
,6
]}

Berndt, Sarah ^{[4
,5
,6
]}

Novais, Anita ^{[1
,2
]}

Lesage, Matthieu ^{[4
,5
,6
]}

Hosten, Benoit ^{[7
]}

Vercellino, Laetitia ^{[8
]}

Merlet, Pascal ^{[8
]}

Le-Denmat, Dominique ^{[1
,2
]}

Marchiol, Carmen ^{[9
]}

Letourneur, Didier ^{[10
,11
]}

Nicoletti, Antonino ^{[10
,11
]}

Vital, Sibylle Opsahl ^{[1
,2
,3
]}

Poliard, Anne ^{[1
,2
]}

Salmon, Benjamin ^{[1
,2
,3
]}

Muller, Laurent ^{[4
,5
,6
]}

Chaussain, Catherine ^{[1
,2
,3
]}

Germain, Sttphane ^{[4
,5
,6
]}

机构：

[1] Univ Paris 05, Sorbonne Paris Cite, EA Pathol Imagerie & Biotherapies Orofaciales 249, F-92120 Montrouge, France

[2] Univ Paris 05, Sorbonne Paris Cite, Sch Dent, Plateforme Imagerie Vivant, F-92120 Montrouge, France

[3] Hop Univ PNVS, AP HP, Dept Odontol, Paris, France

[4] Coll France, Ctr Interdisciplinary Res Biol, F-75231 Paris, France

[5] INSERM, U1050, Paris, France

[6] CNRS, UMRS 7241, Paris, France

[7] Univ Paris 05, Paris Diderot Sorbonne Paris Cite, Hop St Louis, AP HP,Unite Claude Kellershohn,INSERM,UMR S1144, F-92120 Paris, France

[8] Univ Paris Diderot, Hop St Louis, AP HP, Unite Claude Kellershohn, F-92120 Paris, France

[9] Univ Paris Diderot, Hop St Louis, Inst Cochin, Plateforme Imagerie Vivant, F-92120 Paris, France

[10] Univ Paris Diderot, Sorbonne Paris Cite, Lab Vasc Translat Sci, INSERM,U1148,Fac Med,Site Xavier Bichat, F-92120 Paris, France

[11] Dept Hospitalo Univ Fibrosis, Inflammat & Remodeling, Paris, France

来源：

STEM CELLS TRANSLATIONAL MEDICINE | 2016年 / 5卷 / 03期

关键词：

Pulp engineering; Mesenchymal stem cells; Hypoxia; Angiogenesis; Dynamic vascular imaging; Vascular endothelial growth factor; Hepatocyte growth factor; EXFOLIATED DECIDUOUS TEETH; SIDE POPULATION CELLS; IN-VITRO; LIMB ISCHEMIA; STROMAL CELLS; HYPOXIA; VIVO; DIFFERENTIATE; COLLAGEN; VEGF;

D O I：

10.5966/sctm.2015-0166

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF.

引用

页码：392 / 404

页数：13

共 64 条

[1]

Hypoxia Enhances the Angiogenic Potential of Human Dental Pulp Cells [J].