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: 1703570
• 负责人: Feng Zhao
• 金额: $ 31万
• 依托单位: Michigan Technological University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1703570&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.

替换病变组织要求植入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配网络（脉管系统；静脉、毛细血管），而这些通常难以制造。该项目将寻求理解和模拟三维（3D）心脏组织的结构和脉管系统。目标是设计一种机械强度高且功能齐全的细胞补片，用于受损心脏组织的再生。拟议的研究还将为本科生和研究生以及代表性不足的社区学院学生提供参与跨学科干细胞和组织工程研究的机会。此外，还将举办一系列研讨会，以提高密歇根州 UP（上半岛）卫生界和公众对干细胞和组织工程的认识。该项目的总体目标是创建对齐的纳米纤维天然细胞外基质（ECM）支架，用于预血管化各向异性干细胞贴片的生物制造，并阐明体内微环境中微血管定向的机制。人间充质干细胞（hMSC）具有免疫调节、再生能力，可有效促进心肌再生，并作为周细胞发挥稳定内皮细胞（EC）形成的微血管的作用。这些独特的特性使 hMSC 能够与 ECM 支架和 EC 结合，生物制造现成的或患者特异性的预血管化补片，其中 hMSC 将发挥双重作用，稳定 EC 体外形成的血管系统，并协调死亡心脏的再生。植入后的组织。在该项目中，hMSCs将与ECs在纳米纤维ECM支架中共培养，形成对齐的毛细血管样脉管系统，并将研究对齐的纳米纤维对微血管的密度、方向和成熟的影响。预血管化的 hMSC 片将在灌注生物反应器中进行多层化并进一步成熟，并且将评估生理间质流对 3D 仿生组织平台内现有微血管的互连、排列和成熟的作用。如果成功，该项目可能会导致个性化或现成的心脏组织补片的开发，从而大大提高治疗与心脏病发作相关的死亡心肌的成功率。

项目成果

Protocols for Full Thickness Skin Wound Repair Using Prevascularized Human Mesenchymal Stem Cell Sheet

使用预血管化人间充质干细胞片修复全层皮肤伤口的方案

• DOI: 10.1007/7651_2018_142
• 发表时间: 2018-04
• 期刊: Methods in molecular biology
• 作者: Lei Chen; Daniel Radke
• 通讯作者: Daniel Radke

Mesenchymal stem cells for pre-vascularization of engineered tissues

间充质干细胞用于工程组织的预血管化

• DOI: 10.15406/jsrt.2018.04.00112
• 发表时间: 2018-04-19
• 期刊: Journal of Stem Cell Research & Therapeutics
• 作者: Dhavan Sharma;Juan Chica;F. Zhao
• 通讯作者: F. Zhao

Preservation of microvascular integrity and immunomodulatory property of prevascularized human mesenchymal stem cell sheets

预血管化人间充质干细胞片的微血管完整性和免疫调节特性的保存

• DOI: 10.1002/term.3167
• 发表时间: 2021-01-11
• 期刊: Journal of Tissue Engineering and Regenerative Medicine
• 影响因子: 3.3
• 作者: Wenkai Jia;Dhavan Sharma;Weilue He;Qi Xing;F. Zhao
• 通讯作者: F. Zhao

Polydopamine and collagen coated micro-grated polydimethylsiloxane for human mesenchymal stem cell culture

用于人间充质干细胞培养的聚多巴胺和胶原涂层微磨聚二甲基硅氧烷

• DOI: 10.1016/j.bioactmat.2019.02.002
• 发表时间: 2019-02-21
• 期刊: Bioactive Materials
• 影响因子: 18.9
• 作者: Dhavan Sharma;Wenkai Jia;Fei Long;Shweta Pati;Qinghui Chen;Y. Qyang;Bruce P. Lee;C. K. Choi;F. Zhao
• 通讯作者: F. Zhao

Upgrading prevascularization in tissue engineering: A review of strategies for promoting highly organized microvascular network formation

升级组织工程中的预血管化：促进高度组织化微血管网络形成的策略综述

• DOI: 10.1016/j.actbio.2019.03.016
• 发表时间: 2019-03
• 期刊: Acta Biomaterialia
• 影响因子: 9.7
• 作者: Sharma, Dhavan;Ross, David;Wang, Guifang;Jia, Wenkai;Kirkpatrick, Sean J.;Zhao, Feng
• 通讯作者: Zhao, Feng