Research Initiation Award: Optimization and Enhancement of Hepatic Differentiation for Mesenchymal Stem Cells via Biofunctional Modification

研究启动奖：通过生物功能修饰优化和增强间充质干细胞的肝分化

• 批准号: 1946389
• 负责人: Bo Wang
• 金额: $ 26.27万
• 依托单位: Medical College of Wisconsin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-26 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1946389&HistoricalAwards=false
• 关键词: Research; Initiation; Award; Optimization; Enhancement

The Historically Black Colleges and Universities-Undergraduate Program (HBCU-UP) Research Initiation Awards (RIAs) provide support to STEM junior faculty at HBCUs who are starting to build a research program, as well as for mid-career faculty who may have returned to the faculty ranks after holding an administrative post or who need to redirect and rebuild a research program. Faculty members may pursue research at their home institution, at an NSF-funded Center, at a research intensive institution or at a national laboratory. The RIA projects are expected to help further the faculty member's research capability and effectiveness, to improve research and teaching at his or her home institution, and to involve undergraduate students in research experiences. With support from the National Science Foundation, Alabama State University (ASU) will conduct research to address the current lack of ideal cell source for the therapy of hepatocyte transplantation (HT), which is considered as an alternative "bridge" treatment to liver transplantation until a donor liver becomes available. This project plans to create a new cell culture platform to better control stem cell behavior, leading to a possible solution to the shortage of hepatocytes for hepatocyte transplantation treatment. Non-human (porcine) hepatocytes will be used as a source of liver cells for this study. This project will enhance the academic capabilities and outreach activities at ASU. It will provide new research and educational resources for the newly established bachelor's degree program in Biomedical Engineering (BME). Undergraduate students will be afforded the opportunity to participate in various research projects and obtain training in cutting-edge research. These experiences will equip them with the skills necessary to become nationally competitive and prepare them for advanced studies and future careers in STEM. The proposed research is aligned with the mission of the BME program to produce high quality graduates with superior technical, professional, and scientific backgrounds in biomedicine. The goal of this study is to develop a novel cell culture microenvironment by combining a structure-controlled synthetic scaffold with biologically active matrix co-cultured with nonparenchymal cells to positively manipulate stem cell destiny. The specific aims of this project are to: 1) functionalize the multi-layered bioplotted scaffold with liver extracellular matrix (ECM) and signaling peptides to modulate hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs); and 2) characterize the influence of hepatic stellate cells on BM-MSC-derived hepatocytes in vitro and in vivo. The proposed project combines 3D bioprinting and matrix remodeling with liver ECM proteins, signaling peptides, and nonparenchymal cells to create a functionally and structurally natural liver microenvironment. The findings from this study will provide a great step towards positively impacting patients with end-stage liver diseases. In addition, knowledge gained from the proposed research will be applied to the advancement of liver regenerative medicine, as well as to furthering the understanding of fundamental bioengineering techniques. This project will be conducted in collaboration with Northwestern University.

历史上的黑人学院和大学本科生计划（HBCU-UP）研究启动奖（RIAs）为HBCU的STEM初级教师提供支持，他们开始建立研究计划，以及职业生涯中期的教师，他们可能在担任行政职务或需要重新定向和重建研究计划后返回教师队伍。教师可以在他们的家乡机构，在NSF资助的中心，在研究密集型机构或在国家实验室进行研究。RIA项目预计将有助于进一步提高教师的研究能力和效率，改善他或她的家乡机构的研究和教学，并让本科生参与研究经验。在美国国家科学基金会的支持下，亚拉巴马州立大学（ASU）将开展研究，以解决目前缺乏理想的肝细胞移植（HT）治疗细胞来源的问题，HT被认为是肝移植的替代“桥梁”治疗，直到供体肝脏可用。该项目计划创建一个新的细胞培养平台，以更好地控制干细胞行为，从而为肝细胞移植治疗中肝细胞短缺问题提供可能的解决方案。非人（猪）肝细胞将用作本研究的肝细胞来源。该项目将提高亚利桑那州立大学的学术能力和外联活动。它将为新设立的生物医学工程（BME）学士学位课程提供新的研究和教育资源。本科生将有机会参加各种研究项目，并获得尖端研究的培训。这些经验将使他们具备必要的技能，成为国家竞争力，并为他们在干先进的研究和未来的职业生涯做好准备。拟议的研究与BME计划的使命一致，以培养具有生物医学上级技术，专业和科学背景的高质量毕业生。本研究的目标是开发一种新的细胞培养微环境，通过将结构控制的合成支架与非实质细胞共培养的生物活性基质相结合，以积极操纵干细胞的命运。本项目的具体目标是：1）用肝细胞外基质（ECM）和信号肽功能化多层生物绘图支架，以调节骨髓间充质干细胞（BM-MSC）的肝分化; 2）在体外和体内表征肝星状细胞对BM-MSC衍生的肝细胞的影响。该项目将3D生物打印和基质重塑与肝脏ECM蛋白，信号肽和非实质细胞相结合，以创建功能和结构天然的肝脏微环境。这项研究的结果将为积极影响终末期肝病患者迈出重要一步。此外，从拟议的研究中获得的知识将应用于肝脏再生医学的发展，以及进一步了解基础生物工程技术。该项目将与西北大学合作进行。