globalchange  > 全球变化的国际研究计划
项目编号: 1606128
项目名称:
Uncovering Regeneration-Permissive Cues in Lower Vertebrate Retina to Inform Retinal Regenerative Medicine
作者: Rebecca Carrier
承担单位: Northeastern University
批准年: 2016
开始日期: 2016-09-01
结束日期: 2019-08-31
资助金额: 449992
资助来源: US-NSF
项目类别: Standard Grant
国家: US
语种: 英语
特色学科分类: Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
英文关键词: retina ; cell response ; mammalian retina ; vertebrate regeneration-permissive retinal microenvironment ; vertebrate retinal matrix ; future retinal regeneration strategy ; rebecca l. retinal degeneration ; regenerative medicine ; vertebrate matrix composition ; tissue/matrix/soluble factor cue ; adult mammalian retina ; vertebrate species ; human retina ; mammalian retinal progenitor cell ; vertebrate retina ; insoluble cue
英文摘要: 1606128
Carrier, Rebecca L.

Retinal degeneration, particularly associated with aging, is a widespread and increasing health problem currently affecting 2.1 million people in the U.S. and imposing a substantial burden on the economy (~$2 billion annually). It is the leading cause of blindness worldwide. Cell transplantation strategies have shown tremendous promise, but are significantly limited by low levels of cell survival and integration (<1%). The proposed studies aim to elucidate the chemical and physical cues required to enable survival and integration of transplanted cells. This fundamental, quantitative understanding will provide a framework to guide future retinal regeneration strategies and design of materials to serve as effective cell delivery vehicles. The proposed project will also nurture a cohesive education plan including teaching and learning across education levels spanning from K-12 to postgraduate.

While the retinas of some lower vertebrate species do regenerate, the human retina does not. The role of lower vertebrate matrix composition, structure, and mechanical properties in tissue regeneration has not been explored, yet is likely significant and could be exploited to enable significant advances in regenerative medicine. The PI's recent preliminary results indicate that mammalian retinal progenitor cells display strikingly different behavior when introduced to the lower vertebrate (axolotl) retina, in a manner analogous to cell transplantation, relative to a mammalian retina. Specifically, the RPCs in the lower vertebrate retina exhibit markedly enhanced cell survival and integration into the retina - processes central to regeneration. This project will analyze the chemical and physical features of the lower vertebrate regeneration-permissive retinal microenvironment compared to that of adult mammalian retina. The research will include an in-depth study of human retinal progenitor cell response to lower vertebrate retinal matrix, including attachment, survival, differentiation and 3D migration, processes essential to successful cell transplantation strategies. The study will analyze cell response to both intact tissue and decellularized matrix, in the presence and absence of tissue-conditioned medium, to parse effects of cellular vs. acellular (matrix) components and soluble vs. insoluble cues. Importantly, an integrated systems-biology approach will quantitatively relate cell response to tissue/matrix/soluble factor cues and cell signaling events. This quantitative mechanistic understanding will provide a framework to guide future retinal regeneration strategies and biomaterial design.
This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Biomaterials Program of the Division of Materials Research.
资源类型: 项目
标识符: http://119.78.100.158/handle/2HF3EXSE/91373
Appears in Collections:全球变化的国际研究计划
科学计划与规划

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Rebecca Carrier. Uncovering Regeneration-Permissive Cues in Lower Vertebrate Retina to Inform Retinal Regenerative Medicine. 2016-01-01.
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