Establishment of a Cochlear Organoid Platform for Remodeling the Extracellular Matrix

被引：0

作者：

Li, Nianci ^{[1
]}

Zhang, Ziyu ^{[1
]}

Zhang, Liyan ^{[1
]}

Wu, Danqi ^{[1
]}

Li, Zhe ^{[2
,4
]}

Xu, Changling ^{[5
]}

Sun, Qiuhan ^{[1
]}

Lu, Yicheng ^{[1
]}

Zhou, Yinyi

Qian, Xiaoyun ^{[6
]}

Hu, Yangnan ^{[1
,7
]}

Tan, Fangzhi ^{[1
]}

Qi, Jieyu ^{[2
,3
,8
]}

Chai, Renjie ^{[1
,5
,7
,9
]}

机构：

[1] Southeast Univ, Zhongda Hosp,Dept Otolaryngol Head & Neck Surg, Sch Life Sci & Technol,State Key Lab Digital Med E, Adv Inst Life & Hlth,Jiangsu Prov High Tech Key La, Nanjing 210096, Peoples R China

[2] Beijing Inst Technol, Zhuhai Peoples Hosp, Adv Technol Res Inst, Affiliated Hosp,Dept Radiol,Sch Life Sci, Beijing 100081, Peoples R China

[3] Beijing Inst Technol, State Key Lab Hearing & Balance Sci, Beijing 100081, Peoples R China

[4] Beijing Inst Technol, Beijing 100081, Peoples R China

[5] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sch Med, Dept Otolaryngol Head & Neck Surg, Chengdu 610072, Peoples R China

[6] Nanjing Univ, Dept Otolaryngol Head & Neck Surg, Jiangsu Prov Key Med Discipline Lab, Affiliated Nanjing Drum Tower Hosp,Med Sch, Nanjing 210008, Peoples R China

[7] Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China

[8] Beijing Inst Technol Jinan, Adv Technol Res Inst, Jinan 250307, Peoples R China

[9] Southeast Univ, Shenzhen Res Inst, Shenzhen 518063, Peoples R China

来源：

ACS NANO | 2025年

基金：

北京市自然科学基金; 中国国家自然科学基金; 中国博士后科学基金;

关键词：

cochlear organoids; GelMA hydrogel; extracellularmatrix remodeling; Mmps; hair cell differentiation; HAIR-CELLS; SUPPORTING CELLS; INNER-EAR; METALLOPROTEINASES; GENERATION; EXPRESSION; CULTURE; GENES;

D O I：

10.1021/acsnano.5c04897

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Irreparable injury and depletion of inner ear hair cells lead to permanent hearing impairment. Cochlear organoids serve as a robust in vitro platform for investigating the pathogenesis of deafness and exploring therapeutic approaches. However, the widely used commercial Matrigel in cochlear organoid culture suffers from issues related to consistency and structural stability. Here, we developed a cochlear organoid culture system using synthetic GelMA hydrogel, which promoted the spontaneous clustering and organization of cochlear stem cells, thereby accelerating organoid formation and facilitating the functional maturation of cochlear hair cells. Moreover, we observed that the extracellular matrix (ECM) underwent rapid and extensive remodeling during the early phase of organoid self-organization. During cochlear organoid development, matrix metalloproteinases (Mmps) were markedly upregulated, with Mmp9 displaying relatively higher expression. Notably, inhibition of Mmps significantly interfered with the organoid formation process, suggesting their important role in cochlear organoid morphogenesis. Collectively, this work provides an alternative approach for cochlear organoid generation and underscores the contribution of Mmp-mediated ECM remodeling during organoid formation.

引用

页数：20

共 88 条

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