CAREER: Programming Mesenchymal Stem Cell Fate: An Integrated Research and Education Approach

职业：间充质干细胞命运编程：一种综合研究和教育方法

• 批准号: 1346807
• 负责人: Mariah Hahn
• 金额: $ 35.85万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-10 至 2016-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1346807&HistoricalAwards=false
• 关键词: CAREER; Programming; Mesenchymal; Stem; Cell

This Career award by the Biomaterials program in the Materials Research Division to Texas Engineering Experimental Station, College Station is to advance rational scaffold design for organ regeneration and to develop the next generation of tissue engineers. These studies will be carried out with a particular focus on guiding adult mesenchymal stem cell (MSC) differentiation. Growth factors have long been recognized as potent drivers of MSC growth and differentiation. However, recent studies have demonstrated that scaffold stiffness can have a similar degree of influence on MSC differentiation. These findings have opened up the possibility that MSC differentiation can be dictated by tailoring scaffold material properties alone. A complex array of scaffold properties is currently recognized to impact MSC lineage progression. The goal of the proposed studies is to determine the relative influence of these various scaffold properties on MSC differentiation using a novel biomaterial platform based on collagen-mimetic proteins with programmable cell interaction sites. Understanding the dominant scaffold properties in terms of driving specific MSC differentiation will allow focus on optimizing this narrowed scaffold property set when designing scaffolds for organ regeneration. Successful completion of the proposed work is expected to significantly advance the rapid design of tissue scaffolds, leading to improved treatments for organ damage. The proposed education activities focus on increasing the interest and confidence of minorities and young women in STEM at critical periods during which STEM confidence often decreases. These activities include exposing middle school, high school, and undergraduate students to biomaterials and to associated cutting-edge scientific techniques and will advance the next generation of tissue engineers by promoting the increased representation of traditionally underrepresented groups in high-level STEM careers.Tissue engineering holds great promise for the treatment of patients with damaged organs and generally involves combining cells with a biomaterial support. The present proposal encompasses a set of integrated research and education activities designed to dramatically advance biomaterial design for organ regeneration and to develop the next generation of tissue engineers. MSCs are a promising patient-derived cell source that can be induced to differentiate into a range of cell types. However, the ability to control MSC differentiation at a level required for organ regeneration has not yet been achieved. A complex array of biomaterial factors are known to impact MSC differentiation. The goal of the proposed studies is to identify the dominant biomaterial factors in terms of guiding specific MSC differentiation. Understanding the dominant biomaterial influences on MSC differentiation will allow focus on optimizing subset of factors, rather than a broad range of potential factors, when designing biomaterials for organ regeneration. The proposed education plan includes middle school, high school, and undergraduate outreach. The proposed outreach activities focus on increasing the interest and activities of minorities and young women in STEM related topics. The education plan was developed in close consultation with education experts and will advance the next generation of tissue engineers by promoting the increased representation of traditionally underrepresented groups in high-level STEM careers.

这项由材料研究部生物材料项目颁发给德克萨斯工程实验站大学站的职业奖项是为了推进器官再生的合理支架设计，并培养下一代组织工程师。这些研究将特别注重引导成人间充质干细胞(MSC)的分化。长期以来，生长因子一直被认为是骨髓间充质干细胞生长和分化的有力驱动因素。然而，最近的研究表明，支架硬度对MSC的分化也有类似程度的影响。这些发现开启了一种可能性，即仅通过剪裁支架材料的属性就可以决定MSC的差异性。一系列复杂的支架特性目前被认为是影响MSC谱系进展的因素。本研究的目的是利用一种新型的生物材料平台来确定这些不同的支架特性对MSC分化的相对影响，该平台基于具有可编程的细胞相互作用位点的胶原模拟蛋白。了解在驱动特定MSC分化方面的主要支架属性将使我们能够在设计器官再生支架时专注于优化这种狭窄的支架属性集。拟议工作的成功完成预计将大大推进组织支架的快速设计，从而改进器官损伤的治疗方法。拟议的教育活动侧重于在STEM信心经常下降的关键时期增加少数群体和年轻妇女对STEM的兴趣和信心。这些活动包括让初中生、高中生和本科生接触生物材料和相关的尖端科学技术，并将通过促进传统上代表性不足的群体在高水平STEM职业生涯中的更多代表性来推动下一代组织工程师。组织工程学在治疗器官受损患者方面前景光明，通常涉及将细胞与生物材料支架相结合。本提案包括一系列综合研究和教育活动，旨在极大地促进器官再生的生物材料设计，并培养下一代组织工程师。MSCs是一种很有前途的患者来源的细胞来源，可以被诱导分化为一系列细胞类型。然而，将MSC分化控制在器官再生所需的水平上的能力尚未实现。已知一系列复杂的生物材料因素会影响MSC的分化。建议研究的目标是确定在引导特定MSC分化方面的主要生物材料因素。当设计用于器官再生的生物材料时，了解主要的生物材料对MSC分化的影响将使人们能够专注于优化因素子集，而不是广泛的潜在因素。拟议的教育计划包括初中、高中和本科生外展。拟议的外联活动侧重于提高少数群体和年轻妇女对与STEM有关的专题的兴趣和活动。该教育计划是在与教育专家密切协商后制定的，将通过促进传统上代表性不足的群体在高级别STEM职业中的更多代表性来促进下一代组织工程师的发展。