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

历史上的黑人学院和大学本科项目（HBCU-UP）研究启动奖（RIAs）为hbcu中开始建立研究项目的STEM初级教师提供支持，也为那些在担任行政职务后可能已经回到教师队伍或需要重新定向和重建研究项目的职业中期教师提供支持。教师可以在自己的学校、美国国家科学基金会资助的中心、研究密集型机构或国家实验室进行研究。RIA项目将有助于进一步提高教师的研究能力和效率，改善其所在机构的研究和教学，并使本科生参与研究经验。在美国国家科学基金会的支持下，阿拉巴马州立大学（ASU）将开展研究，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另一种“桥梁”治疗，直到供体肝脏可用。本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。非人类（猪）肝细胞将被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展活动。它将为新成立的生物医学工程（BME）学士学位课程提供新的研究和教育资源。本科生将有机会参与各种研究项目，并获得前沿研究方面的培训。这些经历将使他们具备具备全国竞争力所必需的技能，并为他们在STEM领域的深造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，即培养具有卓越技术，专业和科学背景的高素质生物医学毕业生。本研究的目的是通过将结构控制的合成支架与生物活性基质与非实质细胞共培养相结合，开发一种新的细胞培养微环境，以积极地操纵干细胞的命运。该项目的具体目标是：1)利用肝细胞外基质（ECM）和信号肽实现多层生物标记支架的功能化，以调节骨髓间充质干细胞（BM-MSCs）的肝分化；2)在体外和体内研究肝星状细胞对bm - msc源性肝细胞的影响。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结合起来，创造一个功能和结构上自然的肝脏微环境。这项研究的结果将为对终末期肝病患者产生积极影响迈出一大步。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进步，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。

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.