Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix

被引：66

作者：

He, Ling ^{[1
,2
]}

Zhou, Jian ^{[1
,3
]}

Chen, Mo ^{[1
]}

Lin, Chyuan-Sheng ^{[4
]}

Kim, Sahng G. ^{[1
,5
]}

Zhou, Yue ^{[1
,6
]}

Xiang, Lusai ^{[1
,2
]}

Xie, Ming ^{[1
,7
]}

Bai, Hanying ^{[1
]}

Yao, Hai ^{[8
]}

Shi, Changcheng ^{[8
]}

Coelho, Paulo G. ^{[9
]}

Bromage, Timothy G. ^{[9
]}

Hu, Bin ^{[9
]}

Tovar, Nick ^{[9
]}

Witek, Lukasz ^{[9
]}

Wu, Jiaqian ^{[10
]}

Chen, Kenian ^{[10
]}

Gu, Wei ^{[4
]}

Zheng, Jinxuan ^{[1
,2
]}

Sheu, Tzong-Jen ^{[11
]}

Zhong, Juan ^{[1
,2
]}

Wen, Jin ^{[1
,7
]}

Niu, Yuting ^{[1
]}

Cheng, Bin ^{[12
]}

Gong, Qimei ^{[1
,2
]}

Owens, David M. ^{[4
,13
]}

Stanislauskas, Milda ^{[13
]}

Pei, Jasmine ^{[1
]}

Chotkowski, Gregory

Wang, Sainan ^{[1
]}

Yang, Guodong ^{[1
]}

Zegarelli, David J. ^{[5
]}

Shi, Xin ^{[1
]}

Finkel, Myron

Zhang, Wen ^{[1
,2
]}

Li, Junyuan ^{[1
]}

Cheng, Jiayi ^{[1
]}

Tarnow, Dennis P. ^{[5
]}

Zhou, Xuedong ^{[14
]}

Wang, Zuolin ^{[6
]}

Jiang, Xinquan ^{[7
]}

Romanov, Alexander ^{[15
]}

Rowe, David W. ^{[16
]}

Wang, Songlin ^{[3
]}

Ye, Ling ^{[14
]}

Ling, Junqi ^{[2
]}

Mao, Jeremy ^{[1
,4
,5
,17
,18
]}

机构：

[1] Columbia Univ, Ctr Craniofacial Regenerat, New York, NY 10027 USA

[2] Sun Yat Sen Univ, Guangdong Prov Key Lab Stomatol, Operat Dent & Endodont, Affiliated Stomatol Hosp,Guanghua Sch Stomatol, Guangzhou, Guangdong, Peoples R China

[3] Capital Med Univ, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Mol Lab Gene Therapy & Tooth Regenerat, Sch Stomatol, Beijing, Peoples R China

[4] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA

[5] Columbia Univ, Coll Dent Med, New York, NY 10027 USA

[6] Tongji Univ, Sch Stomatol, Dept Conservat Dent, Lab Biomed Sci & Translat Med, Shanghai, Peoples R China

[7] Shanghai Jiao Tong Univ, Dept Prosthodont, Shanghai, Peoples R China

[8] Clemson Univ, Dept Bioengn, Charleston, SC USA

[9] NYU, Dept Biomat & Biomimet, New York, NY USA

[10] Univ Texas Houston, McGovern Med Sch Houston, Vivian L Smith Dept Neurosurg, Ctr Stem Cell & Regenerat Med, Houston, TX USA

[11] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA

[12] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA

[13] Columbia Univ, Dept Dermatol, New York, NY 10027 USA

[14] Sichuan Univ, West China Sch Stomatol, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China

[15] Columbia Univ, Med Ctr, Inst Comparat Med, New York, NY USA

[16] Univ Connecticut, Hlth Sci Ctr, Ctr Regenerat Med & Skeletal Dev, Farmington, CT USA

[17] Columbia Univ Phys & Surg, Dept Orthoped Surg, New York, NY 10032 USA

[18] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA

来源：

NATURE MATERIALS | 2019年 / 18卷 / 06期

基金：

中国国家自然科学基金;

关键词：

PULP STEM-CELLS; DENTAL-PULP; TRANSPLANTATION; MECHANISMS; ORIGIN; WNT;

D O I：

10.1038/s41563-019-0368-6

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070305 [高分子化学与物理];

摘要：

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/beta-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

引用

页码：627 / +

页数：14

共 52 条

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American Dental Association, 2007, 2005 2006 SURV DENT

[2]

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