Journal Article

Lens regeneration using endogenous stem cells with gain of visual function

Jafari, Maryam, Chen, Jiangna, Signer, Robert A. J., Ouyang, Hong, Xu, Yanxin, Shi, William, Qiu, Austin, Zhong, Zheng, Lin, Haotian, Wen, Cindy, Hou, Rui, Huang, Shan, Wang, Yujuan, Maas, Richard L., Liu, Yizhi, Granet, David, Cao, Guiqun, Lin, Danni, Zhong, Sheng, Wu, Frances, Skowronska-Krawczyk, Dorota, Zhu, Jin, Chen, Baoxin, Zhang, Liangfang, Morrison, Sean J., Zhang, Kang, Liu, Xialin, Li, Xuri, Chen, Shuyi, Cai, Huimin, Liu, Zhenzhen, Shang, Fu, Chen, Daniel, Chung, Christopher, Zhang, Ying, Chen, Shaochen, Krawczyk, Michal, Li, Gen, Patel, Sherrina, Luo, Lixia, Heichel, Christopher, Hou, Jiayi, Zhu, Jie

2016

Overview

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. A new procedure for cataract removal that preserves lens epithelial progenitor cells in mammals, which require Pax6 and Bmi1 for their self-renewal, achieves lens regeneration in rabbits, macaques and in infants with cataracts. Sight restoration through cellular regeneration The only current treatment for cataracts, the leading cause of blindness, is to extract the damaged lens surgically and implant an artificial intraocular lens. The technique has its limitations, so there is great interest in the possibility of a regenerative medicine approach. Two papers published in this issue of Nature report advances that could bring that prospect a little closer. Kang Zhang and colleagues isolate mammalian lens epithelial stem/progenitor cells and show that Pax6 and Bmi1 are required for their renewal. They have also developed a removal procedure for cataract-affected tissue that preserves these cells, and achieved lens regeneration in rabbits, macaques and in human infants with cataracts. In the second paper, Kohji Nishida and colleagues describe a protocol for in vitro generation of a self-formed ectodermal autonomous multi-zone (SEAM) from human induced pluripotent stem cells. The SEAM includes distinct cell lineages from the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. Previous experiments had focused mainly on obtaining one cell type. These authors show that cells from the SEAM can be expanded to form a functional corneal epithelium when transplanted to an animal model of blindness.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/532/489 / 692/699/3161/3168 / Analysis / Animals / Care and treatment / Cataract / Cataract - congenital / Cataract - pathology / Cataract - physiopathology / Cataract - therapy / Cataract Extraction / Cataracts / Epithelial Cells - cytology / Epithelial Cells - metabolism / Eye Proteins - metabolism / Eye surgery / Eyes & eyesight / Homeodomain Proteins - metabolism / Homeostasis / Humanities and Social Sciences / Humans / Lens, Crystalline - cytology / Lens, Crystalline - physiology / Macaca / multidisciplinary / Natural environment / Paired Box Transcription Factors - metabolism / PAX6 Transcription Factor / Polycomb Repressive Complex 1 - metabolism / Proto-Oncogene Proteins - metabolism / Recovery of Function / Regeneration - physiology / Repressor Proteins - metabolism / Science / Stem cell research / Stem cells / Stem Cells - cytology / Stem Cells - metabolism / Studies / Surgical techniques / Tissue engineering / Vision, Ocular - physiology