globalchange  > 影响、适应和脆弱性
项目编号: 1508642
项目名称:
UNS: Collaborative Research: Stem Cell-inspired Nanotherapeutics for Regenerative Repair of Elastic Matrix
作者: Anand Ramamurthi
承担单位: Cleveland Clinic Foundation
批准年: 2014
开始日期: 2015-07-01
结束日期: 2018-06-30
资助金额: USD300000
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: investigator ; stem cell ; elastic tissue ; project ; bm-msc ; regenerative elastic matrix repair ; hbm-smc ; new elastic fiber formation ; cell-free regenerative approach ; bm-smc ; biomimetic elastic matrix regenerative repair ; pro-elastin regenerative stimulus ; major elastic blood vessel ; materials research ; elastic fiber assembly ; regenerative effect ; structural repair ; intrinsically-poor auto-regenerative repair ; broad research impact ; elastic matrix ; new elastic fiber ; novel nanotherapeutic approach ; ecm regenerative repair ; unique inter-institutional collaborative training opportunity ; transport systems division ; matrix assembly-impaired phenotype ; elastic matrix regenerative repair
英文摘要: PI: Ramamurthi, Anand/ Rao, Raj R
Proposal Number: 1508642 / 1509377

Restoring structurally damaged soft, elastic tissues to a healthy state is difficult since adult cells are poorly capable of building new elastic fibers, which allow tissues to stretch and recoil. In this project, the investigators propose identification and characterization of factors derived from stem cells towards regenerating and repairing elastic fiber assembly and structure. Further, the studies aim to deliver factors in a sustained manner using degradable polymeric particles which are themselves chemically modified to stimulate new elastic fiber formation and prevent its breakdown. The investigators will then test the effectiveness of the particles in treating abdominal aortic aneurysms, a disorder characterized by breakdown of the structure of the major elastic blood vessel (aorta). In the future, this platform technology can be extended to treat other non-vascular elastic tissue types (e.g., lung tissue) in need of structural repair.

This proposal aims to develop innovative, new approaches to enable in situ, biomimetic elastic matrix regenerative repair in soft, elastic tissues structurally compromised by proteolytic injury. The proposed approach seeks to overcome intrinsically-poor auto-regenerative repair of disrupted elastic matrix by stable adult cell types. The investigators have recently shown bone marrow mesenchymal stem cell (BM-MSC)-derived smooth muscle cells (BM-SMCs), but not undifferentiated BM-MSCs, to be significantly more elastogenic than adult vascular SMCs (healthy, diseased), and their secretions to stimulate elastic matrix regenerative repair by SMCs of a diseased, matrix assembly-impaired phenotype. As physical delivery of stem cells faces several challenges, this project proposes to design and test a stem cell-inspired, but cell-free regenerative approach to in situ ECM regenerative repair. The approach is based on sustained, local delivery of BM-SMC secretome components identified to be necessary and sufficient for pro-elastin regenerative stimulus from novel polymer nanocarriers that themselves exhibit pro-elastogenic and anti-proteolytic properties. Through experiments designed to address three specific aims, the investigators will test hypotheses that a) human BM-MSCs (hBM-MSCs) can be efficiently differentiated into SMCs (hBM-SMCs) exhibiting distinct, elastogenicity-determining phenotypic states; b) pro-elastogenic effects of hBM-SMCs on abdominal aortic aneurysm SMCs are mediated by their secreted trophic factors (secretome); c) key components of hBM-SMC secretome individually or in combination are necessary and sufficient for pro-elastogenic and anti-proteolytic effect; and d) integrating sustained delivery of key hBM-SMC secretome factor(s) with nanocarriers will augment quantity & quality of regenerative elastic matrix repair in an ECM-disrupted, 3-D tissue space. The broad research impact of this project is based on its potential that a novel nanotherapeutic approach may enable regenerative elastic matrix repair that recapitulates regenerative effects of SC secretions. Through this project, the investigators will a) develop educational modules for students at several educational levels to better understand stem cell- and tissue engineering, and b) provide unique inter-institutional collaborative training opportunities for students at Cleveland Clinic and Virginia Commonwealth University. By working through well-established summer internship and outreach programs at these institutions, the investigators will develop educational modules that will benefit high school students, undergraduate students and the general public. This proposal is co-funded by the Biomedical Engineering Program in the Chemical, Bioengineering, Environmental and Transport Systems Division, and by the Biomaterials Program in the Division of Materials Research.
资源类型: 项目
标识符: http://119.78.100.158/handle/2HF3EXSE/94276
Appears in Collections:影响、适应和脆弱性
气候减缓与适应

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Recommended Citation:
Anand Ramamurthi. UNS: Collaborative Research: Stem Cell-inspired Nanotherapeutics for Regenerative Repair of Elastic Matrix. 2014-01-01.
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