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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.

SUBMITTER: Lin H

PROVIDER: S-EPMC6061995 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

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

Nature 20160309 7594

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 sh ...[more]

PMID: 26958831

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Project description:BackgroundThe major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear.MethodsGain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA).ResultsCXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs.ConclusionsCXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.

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

Publications

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

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