Journal article
Photoactivation of Endogenous Latent Transforming Growth Factor-beta 1 Directs Dental Stem Cell Differentiation for Regeneration
Science translational medicine, Vol.6(238), 238ra69
05/28/2014
DOI: 10.1126/scitranslmed.3008234
PMCID: PMC4113395
PMID: 24871130
Abstract
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.
Details
- Title: Subtitle
- Photoactivation of Endogenous Latent Transforming Growth Factor-beta 1 Directs Dental Stem Cell Differentiation for Regeneration
- Creators
- Praveen R. Arany - Harvard UniversityAndrew Cho - National Institute of Dental and Craniofacial ResearchTristan D. Hunt - Harvard UniversityGursimran Sidhu - Harvard UniversityKyungsup Shin - Harvard UniversityEason Hahm - Harvard UniversityGeorge X. Huang - Harvard UniversityJames Weaver - Wyss Institute for Biologically Inspired EngineeringAaron Chih-Hao Chen - Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USABonnie L. Padwa - Boston Children's HospitalMichael R. Hamblin - Harvard–MIT Division of Health Sciences and TechnologyMary Helen Barcellos-Hoff - New York UniversityAshok B. Kulkarni - National Institute of Dental and Craniofacial ResearchDavid J. Mooney - Harvard University
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.6(238), 238ra69
- DOI
- 10.1126/scitranslmed.3008234
- PMID
- 24871130
- PMCID
- PMC4113395
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 11
- Grant note
- R01AI050875 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) 1UL1 TR001102-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA ZIADE000698 / NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) Harvard Presidential Scholarship Harvard University Harvard Clinical and Translational Science Center [National Center for Research Resources (NCRR)] National Center for Advancing Translational Sciences (NCATS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) Wyss institute, Harvard Catalyst R01DE013349 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) UL1TR001102 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Language
- English
- Date published
- 05/28/2014
- Academic Unit
- Orthodontics; Craniofacial Anomalies Research Center
- Record Identifier
- 9984367719502771
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