Photoactivation of Endogenous Latent Transforming Growth Factor-β1 Directs Dental Stem Cell Differentiation for Regeneration

被引：205

作者：

Arany, Praveen R. ^{[1
,2
,3
,4
,5
]}

Cho, Andrew ^{[5
]}

Hunt, Tristan D. ^{[1
]}

Sidhu, Gursimran ^{[1
]}

Shin, Kyungsup ^{[1
,3
]}

Hahm, Eason ^{[1
]}

Huang, George X. ^{[1
]}

Weaver, James ^{[2
]}

Chen, Aaron Chih-Hao ^{[6
]}

Padwa, Bonnie L. ^{[7
]}

Hamblin, Michael R. ^{[6
,8
,9
]}

Barcellos-Hoff, Mary Helen ^{[10
]}

Kulkarni, Ashok B. ^{[5
]}

Mooney, David J. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA

[2] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA

[3] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA

[4] Leder Human Biol & Translat Med, Boston, MA 02115 USA

[5] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA

[6] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA

[7] Childrens Hosp, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA

[9] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[10] NYU, Sch Med, New York, NY 10016 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2014年 / 6卷 / 238期

关键词：

GROWTH-FACTOR-BETA; LEVEL LASER IRRADIATION; IN-VITRO; PULP COMPLEX; BONE-MARROW; ACTIVATION; TGF-BETA-1; AMELOBLASTS; PROTEINS; MATRIX;

D O I：

10.1126/scitranslmed.3008234

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even simpler approaches that use exogenous factors to differentiate tissue-resident stem cells carry significant off-target side effects. We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor-beta 1 (TGF-beta 1), that subsequently differentiates host stem cells to promote tissue regeneration. LPL treatment induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn, activated latent TGF-beta 1 (LTGF-beta 1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-beta 1 was capable of differentiating human dental stem cells in vitro. Further, an in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment. These in vivo effects were abrogated in TGF-LPL-induced receptor II (TGF-beta RII) conditional knockout (DSPP(Cre)TGF-beta RIIfl/fl) mice or when wild-type mice were given a TGF-beta RI inhibitor. These findings indicate a pivotal role for TGF-beta in mediating LPL-induced dental tissue regeneration. More broadly, this work outlines a mechanistic basis for harnessing resident stem cells with a light-activated endogenous cue for clinical regenerative applications.

引用

页数：11

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