Lens regeneration using endogenous stem cells with gain of visual function

Haotian Lin, Hong Ouyang, Jie Zhu, Shan Huang, Zhenzhen Liu, Shuyi Chen, Guiqun Cao, Gen Li, Robert A. J. Signer, Yanxin Xu, Christopher Chung, Ying Zhang, Danni Lin, Sherrina Patel, Frances Wu, Huimin Cai, Jiayi Hou, Cindy Wen, Maryam Jafari, Xialin Liu, Lixia Luo, Jin Zhu, Austin Qiu, Rui Hou, Baoxin Chen, Jiangna Chen, David Granet, Christopher Heichel, Fu Shang, Xuri Li, Michal Krawczyk, Dorota Skowronska-Krawczyk, Yujuan Wang, William Shi, Daniel Chen, Zheng Zhong, Sheng Zhong, Liangfang Zhang, Shaochen Chen, Sean J. Morrison, Richard L. Maas, Kang Zhang () and Yizhi Liu ()
Additional contact information
Haotian Lin: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Hong Ouyang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Jie Zhu: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Shan Huang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Zhenzhen Liu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Shuyi Chen: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Guiqun Cao: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Gen Li: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Robert A. J. Signer: Howard Hughes Medical Institute, Children’s Research Institute, University of Texas Southwestern Medical Center
Yanxin Xu: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Christopher Chung: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Ying Zhang: Brigham and Women’s Hospital and Harvard Medical School
Danni Lin: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Sherrina Patel: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Frances Wu: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Huimin Cai: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Jiayi Hou: Clinical and Translational Research Institute, University of California
Cindy Wen: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Maryam Jafari: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Xialin Liu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Lixia Luo: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Jin Zhu: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Austin Qiu: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Rui Hou: Guangzhou KangRui Biological Pharmaceutical Technology Company
Baoxin Chen: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Jiangna Chen: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
David Granet: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Christopher Heichel: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Fu Shang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Xuri Li: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Michal Krawczyk: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Dorota Skowronska-Krawczyk: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Yujuan Wang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
William Shi: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Daniel Chen: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Zheng Zhong: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Sheng Zhong: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Liangfang Zhang: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Shaochen Chen: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California
Sean J. Morrison: Howard Hughes Medical Institute, Children’s Research Institute, University of Texas Southwestern Medical Center
Richard L. Maas: Brigham and Women’s Hospital and Harvard Medical School
Kang Zhang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Yizhi Liu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University

Nature, 2016, vol. 531, issue 7594, 323-328

Abstract: Abstract The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

Date: 2016
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DOI: 10.1038/nature17181

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