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Nature. 2016 Mar 17;531(7594):323-8. doi: 10.1038/nature17181. Epub 2016 Mar 9.

Lens regeneration using endogenous stem cells with gain of visual function.

Author information

1
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
2
Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
3
Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
4
Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China.
5
Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
6
Department of Ophthalmology, West China Hospital, Sichuan University, Sichuan 610041, China.
7
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
8
Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California 92093, USA.
9
Veterans Administration Healthcare System, San Diego, California 92093, USA.

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.

PMID:
26958831
PMCID:
PMC6061995
DOI:
10.1038/nature17181
[Indexed for MEDLINE]
Free PMC Article

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