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

历史黑人学院和大学-本科项目(HBCU-UP)研究启动奖(RIA)为HBCU的STEM初级教员提供支持，他们开始建立研究项目，以及为职业生涯中期可能在担任行政职位后重返教职队伍或需要重新定向和重建研究项目的教师提供支持。教职员工可以在他们的家乡机构、NSF资助的中心、研究密集型机构或国家实验室进行研究。RIA项目有望帮助教师进一步提高研究能力和效率，改善其所在机构的研究和教学，并让本科生参与研究体验。在美国国家科学基金会的支持下，阿拉巴马州立大学(ASU)将进行研究，以解决目前肝细胞移植(HT)治疗缺乏理想细胞来源的问题。肝细胞移植被认为是肝移植的替代“桥梁”治疗，直到有供体肝脏可用。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的行为，从而可能解决肝细胞移植治疗中肝细胞短缺的问题。非人(猪)肝细胞将被用作本研究的肝细胞来源。该项目将加强亚利桑那州立大学的学术能力和外展活动。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接受尖端研究方面的培训。这些经验将使他们具备必要的技能，使他们在国家中具有竞争力，并为他们在STEM深造和未来的职业生涯做好准备。这项拟议的研究与BME计划的使命相一致，即培养具有卓越的生物医学技术、专业和科学背景的高质量毕业生。本研究的目的是开发一种新型的细胞培养微环境，通过将结构可控的合成支架与生物活性基质与非实质细胞共培养来积极操纵干细胞的命运。本项目的具体目的是：1)将含有肝细胞外基质(ECM)和信号肽的多层生物标示支架功能化，以调节骨髓间充质干细胞(BM-MSCs)的肝脏分化；2)研究肝星状细胞对BM-MSC来源的肝细胞的影响。拟议的项目结合了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，以创造一个功能和结构上自然的肝脏微环境。这项研究的发现将向对终末期肝病患者产生积极影响的方向迈出一大步。此外，从拟议研究中获得的知识将应用于肝脏再生医学的发展，以及加深对基本生物工程技术的理解。该项目将与西北大学合作进行。

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.