Engineering vascularised and aligned tissues using ultrasound cell patterning

使用超声细胞图案设计血管化和排列的组织

• 批准号: MR/S00551X/1
• 负责人: James Armstrong
• 金额: $ 77.7万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS00551X%2F1
• 关键词: Engineering; vascularised; aligned; tissues; using

Over the last 25 years, scientists have developed methods for growing tissues (e.g. muscle, cartilage), which can be used to replace diseased or injured tissue, or as a tool for testing drugs. Unfortunately, these laboratory-grown tissues do not perform as well as natural tissue. One of the main reasons for this is that it is very difficult to recreate the particular organization of natural tissues. For example, muscle is made up of bundles of aligned cells; an organization that allows it to contract and relax in the same direction. We have shown that we can partially recreate this organization using a technique known as "ultrasound cell patterning". Here, we use ultrasound to remotely move cells into parallel lines; this is very quick (< 5 min) and has very little affect on the health of the cells. We first used ultrasound to pattern lines of muscle cells, which were then set into a collagen gel to preserve the cell pattern. We grew these muscle gels in the laboratory for seven days to form muscle with bundles of aligned muscle cells; just like in natural muscle. These early results are very promising, but there are several ways that it can be improved:(1) In the early results, we showed that muscle cells could be patterned in 2D lines, however, muscle is made of 3D fibres. The first aim of this work will be to add another ultrasound wave to create 3D tubes of muscle cells, so that we can grow 3D muscle.(2) Currently we can only do the cell patterning once, per tissue. The second aim of this work will be to develop a way of patterning cells layer by layer. This will allow us to add blood vessels, to supply oxygen, in between layers of muscle.(3) The early work used mouse muscle cells, which are a poor imitation of human muscle. A better option is "human induced pluripotent stem cells," a new type of cell that can be used to make muscle cells. The third aim of this work would be to use these cells to grow patterned muscle.The optimised system will be used in the fourth aim of this research; to engineer laboratory-grown patterned muscle for pharmaceutical drug testing. Specifically, we will study a genetic disease known as muscular dystrophy, which causes muscle wastage and degeneration. The final aim of this work is to develop these tools as a platform technology that can be used to grow other organized tissues. This includes cartilage, tendon, ligament and heart tissue.

在过去的25年里，科学家们已经开发出了生长组织（例如肌肉，软骨）的方法，这些组织可以用来替代患病或受伤的组织，或者作为测试药物的工具。不幸的是，这些实验室生长的组织并不像天然组织那样表现良好。其中一个主要原因是，很难重建天然组织的特定组织。例如，肌肉是由一束束排列的细胞组成的;这是一种允许它在同一方向收缩和放松的组织。我们已经证明，我们可以使用一种称为“超声细胞图案化”的技术部分重建这种组织。在这里，我们使用超声波将细胞远程移动到平行线中;这非常快（< 5分钟），对细胞的健康影响很小。我们首先使用超声波来绘制肌肉细胞的线条，然后将其放入胶原凝胶中以保留细胞图案。我们在实验室中培养了这些肌肉凝胶七天，以形成具有成束排列的肌肉细胞的肌肉;就像天然肌肉一样。这些早期的结果非常有希望，但有几种方法可以改进：（1）在早期的结果中，我们表明肌肉细胞可以以2D线条图案化，然而，肌肉是由3D纤维组成的。这项工作的第一个目标是添加另一种超声波来创建肌肉细胞的3D管，以便我们可以生长3D肌肉。(2)目前，我们只能对每个组织进行一次细胞图案化。这项工作的第二个目标是开发一种逐层图案化细胞的方法。这将使我们能够在肌肉层之间添加血管来供应氧气。(3)早期的研究使用的是小鼠肌肉细胞，这是对人类肌肉的拙劣模仿。一个更好的选择是“人类诱导多能干细胞”，这是一种可用于制造肌肉细胞的新型细胞。这项工作的第三个目标是使用这些细胞来生长图案化的肌肉。优化的系统将用于这项研究的第四个目标;设计实验室生长的图案化肌肉用于药物测试。具体来说，我们将研究一种称为肌肉萎缩症的遗传疾病，它会导致肌肉萎缩和退化。这项工作的最终目的是开发这些工具作为一种平台技术，可用于生长其他组织。这包括软骨、肌腱、韧带和心脏组织。

项目成果

In vivo biomolecular imaging of zebrafish embryos using confocal Raman spectroscopy.

使用共焦拉曼光谱法对斑马鱼胚胎的体内生物分子成像。

• DOI: 10.1038/s41467-020-19827-1
• 发表时间: 2020-12-02
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Høgset H;Horgan CC;Armstrong JPK;Bergholt MS;Torraca V;Chen Q;Keane TJ;Bugeon L;Dallman MJ;Mostowy S;Stevens MM
• 通讯作者: Stevens MM

A blueprint for translational regenerative medicine.

• DOI: 10.1126/scitranslmed.aaz2253
• 发表时间: 2020-12-02
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Armstrong JPK;Keane TJ;Roques AC;Patrick PS;Mooney CM;Kuan WL;Pisupati V;Oreffo ROC;Stuckey DJ;Watt FM;Forbes SJ;Barker RA;Stevens MM
• 通讯作者: Stevens MM

Engineering Anisotropic Muscle Tissue using Acoustic Cell Patterning.

• DOI: 10.1002/adma.201802649
• 发表时间: 2018-10
• 期刊: Advanced materials (Deerfield Beach, Fla.)
• 作者: Armstrong JPK;Puetzer JL;Serio A;Guex AG;Kapnisi M;Breant A;Zong Y;Assal V;Skaalure SC;King O;Murty T;Meinert C;Franklin AC;Bassindale PG;Nichols MK;Terracciano CM;Hutmacher DW;Drinkwater BW;Klein TJ;Perriman AW;Stevens MM
• 通讯作者: Stevens MM