Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration.

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-β1 (TGF-β1), 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-β1 (LTGF-β1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-β1 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-β receptor II (TGF-βRII) conditional knockout (DSPP(Cre)TGF-βRII(fl/fl)) mice or when wild-type mice were given a TGF-βRI inhibitor. These findings indicate a pivotal role for TGF-β 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.

journal_name

Sci Transl Med

authors

Arany PR,Cho A,Hunt TD,Sidhu G,Shin K,Hahm E,Huang GX,Weaver J,Chen AC,Padwa BL,Hamblin MR,Barcellos-Hoff MH,Kulkarni AB,J Mooney D

doi

10.1126/scitranslmed.3008234

subject

Has Abstract

pub_date

2014-05-28 00:00:00

pages

238ra69

issue

238

eissn

1946-6234

issn

1946-6242

pii

6/238/238ra69

journal_volume

6

pub_type

杂志文章
  • Development of personalized tumor biomarkers using massively parallel sequencing.

    abstract::Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000702

    authors: Leary RJ,Kinde I,Diehl F,Schmidt K,Clouser C,Duncan C,Antipova A,Lee C,McKernan K,De La Vega FM,Kinzler KW,Vogelstein B,Diaz LA Jr,Velculescu VE

    更新日期:2010-02-24 00:00:00

  • Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.

    abstract::Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aal2774

    authors: Hoyle NP,Seinkmane E,Putker M,Feeney KA,Krogager TP,Chesham JE,Bray LK,Thomas JM,Dunn K,Blaikley J,O'Neill JS

    更新日期:2017-11-08 00:00:00

  • Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions.

    abstract::The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic D...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002001

    authors: Dombrowski Y,Peric M,Koglin S,Kammerbauer C,Göss C,Anz D,Simanski M,Gläser R,Harder J,Hornung V,Gallo RL,Ruzicka T,Besch R,Schauber J

    更新日期:2011-05-11 00:00:00

  • Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates.

    abstract::Nonalcoholic fatty liver disease (NAFLD) is estimated to affect up to one-third of the general population, and new therapies are urgently required. Our laboratory previously developed a controlled-release mitochondrial protonophore (CRMP) that is functionally liver-targeted and promotes oxidation of hepatic triglyceri...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aay0284

    authors: Goedeke L,Peng L,Montalvo-Romeral V,Butrico GM,Dufour S,Zhang XM,Perry RJ,Cline GW,Kievit P,Chng K,Petersen KF,Shulman GI

    更新日期:2019-10-02 00:00:00

  • Nonhuman primates exposed to Zika virus in utero are not protected against reinfection at 1 year postpartum.

    abstract::There is limited information about the impact of Zika virus (ZIKV) exposure in utero on the anti-ZIKV immune responses of offspring. We infected six rhesus macaque dams with ZIKV early or late in pregnancy and studied four of their offspring over the course of a year postpartum. Despite evidence of ZIKV exposure in ut...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaz4997

    authors: Vannella KM,Stein S,Connelly M,Swerczek J,Amaro-Carambot E,Coyle EM,Babyak A,Winkler CW,Saturday G,Gai ND,Hammoud DA,Dowd KA,Valencia LP,Ramos-Benitez MJ,Kindrachuk J,Pierson TC,Peterson KE,Brenchley JM,Whitehead SS,

    更新日期:2020-10-28 00:00:00

  • Imaging approaches to optimize molecular therapies.

    abstract::Imaging, including its use for innovative tissue sampling, is slowly being recognized as playing a pivotal role in drug development, clinical trial design, and more effective delivery and monitoring of molecular therapies. The challenge is that, while a considerable number of new imaging technologies and new targeted ...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aaf3936

    authors: Weissleder R,Schwaiger MC,Gambhir SS,Hricak H

    更新日期:2016-09-07 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract::Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000522

    authors: Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期:2010-04-21 00:00:00

  • Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This st...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaz0463

    authors: Vadakekolathu J,Minden MD,Hood T,Church SE,Reeder S,Altmann H,Sullivan AH,Viboch EJ,Patel T,Ibrahimova N,Warren SE,Arruda A,Liang Y,Smith TH,Foulds GA,Bailey MD,Gowen-MacDonald J,Muth J,Schmitz M,Cesano A,Pockley

    更新日期:2020-06-03 00:00:00

  • Off-target lapatinib activity sensitizes colon cancer cells through TRAIL death receptor up-regulation.

    abstract::Lapatinib, a dual HER2/EGFR (human epidermal growth factor receptor 2/epidermal growth factor receptor) inhibitor, is a recently approved targeted therapy for metastatic breast cancer. Because lapatinib enhances the efficacy of the chemotherapeutic agent capecitabine in breast cancer patients, we tested whether lapati...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3001384

    authors: Dolloff NG,Mayes PA,Hart LS,Dicker DT,Humphreys R,El-Deiry WS

    更新日期:2011-06-08 00:00:00

  • Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome.

    abstract::Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aat4822

    authors: Habashi JP,MacFarlane EG,Bagirzadeh R,Bowen C,Huso N,Chen Y,Bedja D,Creamer TJ,Rykiel G,Manning M,Huso D,Dietz HC

    更新日期:2019-05-01 00:00:00

  • PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL+ human leukemia.

    abstract::Overcoming drug resistance and targeting leukemic stem cells (LSCs) remain major challenges in curing BCR-ABL+ human leukemia. Using an advanced drug/proliferation screen, we have uncovered a prosurvival role for protein phosphatase 2A (PP2A) in tyrosine kinase inhibitor (TKI)-insensitive leukemic cells, regulated by ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aan8735

    authors: Lai D,Chen M,Su J,Liu X,Rothe K,Hu K,Forrest DL,Eaves CJ,Morin GB,Jiang X

    更新日期:2018-02-07 00:00:00

  • Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD.

    abstract::Attention deficit hyperactivity disorder (ADHD) is a common and persistent condition characterized by developmentally atypical and impairing inattention, hyperactivity, and impulsiveness. We identified de novo and rare copy number variations (CNVs) in 248 unrelated ADHD patients using million-feature genotyping arrays...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002464

    authors: Lionel AC,Crosbie J,Barbosa N,Goodale T,Thiruvahindrapuram B,Rickaby J,Gazzellone M,Carson AR,Howe JL,Wang Z,Wei J,Stewart AF,Roberts R,McPherson R,Fiebig A,Franke A,Schreiber S,Zwaigenbaum L,Fernandez BA,Roberts W

    更新日期:2011-08-10 00:00:00

  • Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis.

    abstract::Macrophages in the healthy intestine are highly specialized and usually respond to the gut microbiota without provoking an inflammatory response. A breakdown in this tolerance leads to inflammatory bowel disease (IBD), but the mechanisms by which intestinal macrophages normally become conditioned to promote microbial ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aao4755

    authors: Scott NA,Andrusaite A,Andersen P,Lawson M,Alcon-Giner C,Leclaire C,Caim S,Le Gall G,Shaw T,Connolly JPR,Roe AJ,Wessel H,Bravo-Blas A,Thomson CA,Kästele V,Wang P,Peterson DA,Bancroft A,Li X,Grencis R,Mowat AM,Hal

    更新日期:2018-10-24 00:00:00

  • Wnt proteins promote bone regeneration.

    abstract::The Wnt signaling pathway plays a central role in bone development and homeostasis. In most cases, Wnt ligands promote bone growth, which has led to speculation that Wnt factors could be used to stimulate bone healing. We gained insights into the mechanism by which Wnt signaling regulates adult bone repair through the...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000231

    authors: Minear S,Leucht P,Jiang J,Liu B,Zeng A,Fuerer C,Nusse R,Helms JA

    更新日期:2010-04-28 00:00:00

  • Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

    abstract::Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision thro...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa8791

    authors: Ashtari M,Zhang H,Cook PA,Cyckowski LL,Shindler KS,Marshall KA,Aravand P,Vossough A,Gee JC,Maguire AM,Baker CI,Bennett J

    更新日期:2015-07-15 00:00:00

  • Key elements for nourishing the translational research environment.

    abstract::Translation in an academic environment requires a support system--people, goals, models, partnerships, and infrastructures--that will push promising basic science and technology projects forward into the clinic. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa2049

    authors: Volk HD,Stevens MM,Mooney DJ,Grainger DW,Duda GN

    更新日期:2015-04-08 00:00:00

  • Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.

    abstract::Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of nonhuman...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aad3231

    authors: Furlan SN,Watkins B,Tkachev V,Flynn R,Cooley S,Ramakrishnan S,Singh K,Giver C,Hamby K,Stempora L,Garrett A,Chen J,Betz KM,Ziegler CG,Tharp GK,Bosinger SE,Promislow DE,Miller JS,Waller EK,Blazar BR,Kean LS

    更新日期:2015-11-25 00:00:00

  • A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components.

    abstract::Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which resistance emerges through EGFR-independent mechanisms, such as through pathways that promote epithelial-to-mesenchymal transition (EMT). Through a...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaz4589

    authors: Nilsson MB,Sun H,Robichaux J,Pfeifer M,McDermott U,Travers J,Diao L,Xi Y,Tong P,Shen L,Hofstad M,Kawakami M,Le X,Liu X,Fan Y,Poteete A,Hu L,Negrao MV,Tran H,Dmitrovsky E,Peng D,Gibbons DL,Wang J,Heymach JV

    更新日期:2020-09-02 00:00:00

  • Exploiting an Asp-Glu "switch" in glycogen synthase kinase 3 to design paralog-selective inhibitors for use in acute myeloid leukemia.

    abstract::Glycogen synthase kinase 3 (GSK3), a key regulatory kinase in the wingless-type MMTV integration site family (WNT) pathway, is a therapeutic target of interest in many diseases. Although dual GSK3α/β inhibitors have entered clinical trials, none has successfully translated to clinical application. Mechanism-based toxi...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aam8460

    authors: Wagner FF,Benajiba L,Campbell AJ,Weïwer M,Sacher JR,Gale JP,Ross L,Puissant A,Alexe G,Conway A,Back M,Pikman Y,Galinsky I,DeAngelo DJ,Stone RM,Kaya T,Shi X,Robers MB,Machleidt T,Wilkinson J,Hermine O,Kung A,St

    更新日期:2018-03-07 00:00:00

  • Astrocytes light up glial heterogeneity.

    abstract::Functionally diverse subpopulations of astrocytes have correlates in the neoplastic adult brain. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aam9858

    authors: Venere M

    更新日期:2017-03-01 00:00:00

  • Therapeutic synergy between tigecycline and venetoclax in a preclinical model of MYC/BCL2 double-hit B cell lymphoma.

    abstract::High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provid...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aan8723

    authors: Ravà M,D'Andrea A,Nicoli P,Gritti I,Donati G,Doni M,Giorgio M,Olivero D,Amati B

    更新日期:2018-01-31 00:00:00

  • KLF6-SV1 drives breast cancer metastasis and is associated with poor survival.

    abstract::Metastasis is the major cause of cancer mortality. A more thorough understanding of the mechanisms driving this complex multistep process will aid in the identification and characterization of therapeutically targetable genetic drivers of disease progression. We demonstrate that KLF6-SV1, an oncogenic splice variant o...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3004688

    authors: Hatami R,Sieuwerts AM,Izadmehr S,Yao Z,Qiao RF,Papa L,Look MP,Smid M,Ohlssen J,Levine AC,Germain D,Burstein D,Kirschenbaum A,DiFeo A,Foekens JA,Narla G

    更新日期:2013-01-23 00:00:00

  • Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure.

    abstract::Urea, the toxic end product of protein catabolism, is elevated in end-stage renal disease (ESRD), although it is unclear whether or how it contributes to disease. Urea can promote the carbamylation of proteins on multiple lysine side chains, including human albumin, which has a predominant carbamylation site on Lys(54...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3005218

    authors: Berg AH,Drechsler C,Wenger J,Buccafusca R,Hod T,Kalim S,Ramma W,Parikh SM,Steen H,Friedman DJ,Danziger J,Wanner C,Thadhani R,Karumanchi SA

    更新日期:2013-03-06 00:00:00

  • Whole-genome sequencing for optimized patient management.

    abstract::Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inherita...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002243

    authors: Bainbridge MN,Wiszniewski W,Murdock DR,Friedman J,Gonzaga-Jauregui C,Newsham I,Reid JG,Fink JK,Morgan MB,Gingras MC,Muzny DM,Hoang LD,Yousaf S,Lupski JR,Gibbs RA

    更新日期:2011-06-15 00:00:00

  • Squeeze-E squeeze-E.

    abstract::Adding an electrical pulse to a microfluidic device that squeezes cells through narrow channels efficiently delivers DNA to the nucleus. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aan0766

    authors: King KR

    更新日期:2017-03-22 00:00:00

  • Self-tanning cells, the new SPF.

    abstract::A skin-penetrant small molecule activates melanin production to protect cells from cancer-inducing ultraviolet damage. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aan8202

    authors: Venere M

    更新日期:2017-07-05 00:00:00

  • Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3.

    abstract::A primary barrier to the success of T cell-recruiting bispecific antibodies in the treatment of solid tumors is the lack of tumor-specific targets, resulting in on-target off-tumor adverse effects from T cell autoreactivity to target-expressing organs. To overcome this, we developed an anti-HER2/CD3 T cell-dependent b...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aat5775

    authors: Slaga D,Ellerman D,Lombana TN,Vij R,Li J,Hristopoulos M,Clark R,Johnston J,Shelton A,Mai E,Gadkar K,Lo AA,Koerber JT,Totpal K,Prell R,Lee G,Spiess C,Junttila TT

    更新日期:2018-10-17 00:00:00

  • Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.

    abstract::Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whe...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008918

    authors: Kvistborg P,Philips D,Kelderman S,Hageman L,Ottensmeier C,Joseph-Pietras D,Welters MJ,van der Burg S,Kapiteijn E,Michielin O,Romano E,Linnemann C,Speiser D,Blank C,Haanen JB,Schumacher TN

    更新日期:2014-09-17 00:00:00

  • Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma.

    abstract::Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, and therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways to overcome resistance, an urgent clinical need in all relapsed/refractory cancers, remains difficult. Through genomic analyses of clini...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aau1167

    authors: Zhang L,Yao Y,Zhang S,Liu Y,Guo H,Ahmed M,Bell T,Zhang H,Han G,Lorence E,Badillo M,Zhou S,Sun Y,Di Francesco ME,Feng N,Haun R,Lan R,Mackintosh SG,Mao X,Song X,Zhang J,Pham LV,Lorenzi PL,Marszalek J,Heffern

    更新日期:2019-05-08 00:00:00

  • The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy.

    abstract::Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aan3464

    authors: Krall JA,Reinhardt F,Mercury OA,Pattabiraman DR,Brooks MW,Dougan M,Lambert AW,Bierie B,Ploegh HL,Dougan SK,Weinberg RA

    更新日期:2018-04-11 00:00:00