Anisotropic Human Mesenchymal Stem Cell Patch with Oriented Vasculature

具有定向脉管系统的各向异性人间充质干细胞贴片

• 批准号: 2106048
• 负责人: Feng Zhao
• 金额: $ 31万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2106048&HistoricalAwards=false
• 关键词: Anisotropic; Human; Mesenchymal; Stem; Cell

Replacement of diseased tissue requires that the implanted material not only have the proper mechanical strength, but it must also have a functioning blood distribution network (vasculature; veins, capillaries), and these are often difficult to manufacture. This project will seek to understand and mimic the structure and vasculature of three-dimensional (3D) cardiac tissue. The goal is to engineer a mechanically strong and functional cell patch for the regeneration of damaged heart tissue. The proposed research will also provide opportunities for undergraduate and graduate students, as well as underrepresented community college students, to be involved in interdisciplinary stem cell and tissue engineering research. In addition, a series of seminars will be hosted to increase stem cell and tissue engineering awareness among the health community and public in the UP (Upper Peninsula) of Michigan. The overall objective of the project is to create aligned nanofibrous natural extracellular matrix (ECM) scaffolds for the biofabrication of a prevascularized anisotropic stem cell patch and elucidate the mechanism of microvessel orientation within the in vivo microenvironment. Human mesenchymal stem cells (hMSCs) are immunoregulatory, regenerative, effective in promoting myocardial regeneration, and function as pericytes to stabilize the microvessels formed by endothelial cells (ECs). These unique properties enable hMSCs to combine with ECM scaffolds and ECs to biofabricate an off-the-shelf or patient-specific prevascularized patch, in which hMSCs will play a dual role of stabilizing vasculature formed by ECs in vitro and orchestrating the regeneration of dead cardiac tissue after implantation. In this project, hMSCs will be co-cultured with ECs in a nanofibrous ECM scaffold to form an aligned capillary-like vasculature, and the effects of aligned nanofibers on the density, orientation and maturation of the microvessels will be investigated. The prevascularized hMSC sheets will be multi-layered and further matured in a perfusion bioreactor, and the role of physiological interstitial flow on the inter-connections, alignment and maturation of the existing microvessels within the 3D biomimetic tissue platform will be evaluated. If successful, this project could lead to the development of personalized or off-the-shelf cardiac tissue patches that could dramatically increase the success rate for the treatment of dead cardiac muscle associated with heart attacks.

替代患病组织要求植入的材料不仅具有适当的机械强度，而且还必须具有功能正常的血液分布网络（脉管系统；静脉，毛细血管），并且通常难以制造这些。该项目将寻求理解和模仿三维（3D）心脏组织的结构和脉管系统。目的是为受损的心脏组织的再生设计一种机械强，功能性的细胞斑块。拟议的研究还将为大学生和研究生以及代表性不足的社区大学生提供机会，以参与跨学科的干细胞和组织工程研究。此外，将举办一系列研讨会，以提高密歇根州UP（上半岛）健康社区和公众之间的干细胞和组织工程意识。该项目的总体目的是创建对齐的纳米纤维自然细胞外基质（ECM）支架，以生物化前体各向异性干细胞贴片，并阐明体内微观环境中微血管方向的机理。人间充质干细胞（HMSC）是免疫调节的，再生的，有效促进心肌再生，并且功能作为周细胞的功能，可稳定由内皮细胞（ECS）形成的微丝。这些独特的特性使HMSC能够与ECM脚手架和ECS结合，以生物生物生物生物生物生物生物生物构造或患者特异性的过度斑块，其中HMSC将在EC在体外稳定稳定血管的双重作用，并在体外和植入后的死亡心脏组织的再生。在该项目中，HMSC将与ECS在纳米纤维ECM支架中共同培养，以形成一个排列的毛细管样脉管系统，并研究对齐的纳米纤维对微绒毛的密度，方向和成熟的影响。预毛的HMSC板将是多层的，并在灌注生物反应器中进一步成熟，并且将评估生理间质流在3D生物含量组织平台内现有微型固定在连接，对齐和成熟的作用。如果成功，该项目可能会导致个性化或现成的心脏组织斑块的发展，这可能会大大提高治疗与心脏病相关的死心肌的成功率。

项目成果

Enhancement of Lymphangiogenesis by Human Mesenchymal Stem Cell Sheet

• DOI: 10.1002/adhm.202200464
• 发表时间: 2022-07-01
• 期刊: ADVANCED HEALTHCARE MATERIALS
• 影响因子: 10
• 作者: Jia, Wenkai;He, Weilue;Zhao, Feng
• 通讯作者: Zhao, Feng

Tissue Engineering-Based Strategies for Diabetic Foot Ulcer Management

• DOI: 10.1089/wound.2021.0081
• 发表时间: 2021-12-22
• 期刊: ADVANCES IN WOUND CARE
• 影响因子: 4.9
• 作者: Chiu, Alvis;Sharma, Dhavan;Zhao, Feng
• 通讯作者: Zhao, Feng