title: Lens regeneration using endogenous stem cells with gain of visual function.
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.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
authors.forename: Guiqun
authors.initials: G
authors.lastname: Cao
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.|Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Robert A J
authors.initials: RA
authors.lastname: Signer
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.|Department of Ophthalmology, West China Hospital, Sichuan University, Sichuan 610041, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chung
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Danni
authors.initials: D
authors.lastname: Lin
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Sherrina
authors.initials: S
authors.lastname: Patel
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Wu
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.|Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Cai
authors.affiliation: Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Hou
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Wen
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Jafari
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xialin
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Luo
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Qiu
authors.affiliation: Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Baoxin
authors.initials: B
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Jiangna
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: David
authors.initials: D
authors.lastname: Granet
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Heichel
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Dorota
authors.initials: D
authors.lastname: Skowronska-Krawczyk
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: William
authors.initials: W
authors.lastname: Shi
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.|Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Shaochen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Maas
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.|Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.|Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.|Veterans Administration Healthcare System, San Diego, California 92093, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002386:Cataract / Q000151:congenital / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002387:Cataract Extraction; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology* / Q000502:physiology*; D008251:Macaca; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020127:Recovery of Function; D012038:Regeneration / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: C489421:Bmi1 protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1