Optimisation of scaffold matrix for epithelial regeneration on tissue engineered airway implants.

组织工程气道植入物上皮再生支架基质的优化。

• 批准号: MR/L002000/1
• 负责人: Nicholas Hamilton
• 金额: $ 28万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL002000%2F1
• 关键词: Optimisation; scaffold; matrix; epithelial; regeneration

Patients who have sustained trauma or required surgery to the voice box and windpipe (larynx or trachea) can develop irreversible scarring leading to severe breathing difficulties that can be life threatening. Whilst conventional treatments are able to reduce scarring and improve breathing it can leave a patient unable to talk or swallow. Furthermore, in a subset of patients reconstruction fails, resulting in severe breathing difficulties and/or the need for a permanent breathing tube to be surgically placed within the neck. Breathing tubes require the patient to nebulise daily and need daily maintenance which can significantly impact on a patient's quality of life. In addition, tracheostomy tubes can be very stigmatising leading to psychological and social problems. The use of new laboratory techniques has made it possible to engineer new organs within the laboratory and transplant them into sufferers to replace the damaged area. Our group has demonstrated the viability of this technology by transplanting the world's first stem-cell grown windpipe in both an adult and a child to replace an irreversible stricture. Despite the clinical success, a number of hurdles exist before this technology can be translated to every day clinical practice, namely there is a pressing need to improve the regeneration of the cells that line the inside of the graft to prevent scarring and help with cough, speech and swallowing. Cells are best grown on protein scaffolds that act as a map to direct the cells where to attach and divide. My project intends to take cells from the lung and grow them on a number of different types of scaffold in order to determine which is the best. This new knowledge will then be applied to regenerate a more robust inner lining within the laboratory. By producing a new lining that can be used as part of a stem cell based windpipe or voice box transplant we hope to greatly improve the safety and outcome of this type of surgery and thus provide new hope to hundreds of desperate sufferers across the UK. This project will take place at University College London (UCL). UCL is amongst the world's premier centres for biomedical research, as confirmed by the results of the UK's latest research assessment exercise (RAE 2008): the numbers of our researchers shown in RAE 2008 to be carrying out world-leading research places UCL among the top universities in the world. In particularly, I will work as part of an established multidisciplinary team already tasked with providing novel therapies for diseased or damaged head and neck tissue which will allow me to draw on a range of expertise and resources unrivalled in any other part of the world.

遭受创伤或需要对喉咙和气管(喉部或气管)进行手术的患者可能会形成不可逆转的疤痕，导致严重的呼吸困难，可能危及生命。虽然传统的治疗方法能够减少疤痕和改善呼吸，但它会使患者无法说话或吞咽。此外，在一部分患者中，重建失败，导致严重的呼吸困难和/或需要通过手术将永久呼吸管放置在颈部。呼吸管需要患者每天雾化，并需要日常维护，这可能会显著影响患者的生活质量。此外，气管切开管可能会非常耻辱，导致心理和社会问题。新实验室技术的使用使在实验室内设计新的器官并将其移植到患者体内以取代受损区域成为可能。我们团队已经通过将世界上第一个干细胞培养的气管移植到成人和儿童身上来取代不可逆转的狭窄，从而证明了这项技术的可行性。尽管临床上取得了成功，但在将这项技术转化为日常临床实践之前，仍存在许多障碍，即迫切需要改善移植物内部细胞的再生，以防止疤痕形成，并有助于咳嗽、说话和吞咽。细胞最适合生长在蛋白质支架上，这种支架充当了指导细胞附着和分裂的地图。我的项目打算从肺中提取细胞，并将它们培养在多种不同类型的支架上，以确定哪种支架是最好的。然后，这一新知识将被应用于在实验室内再生更坚固的内衬。通过生产一种新的衬里，可以用作基于干细胞的气管或声箱移植的一部分，我们希望极大地提高这种类型的手术的安全性和结果，从而为英国数百名绝望的患者带来新的希望。该项目将在伦敦大学学院(UCL)进行。伦敦大学学院是世界一流的生物医学研究中心之一，英国最新的研究评估(RAE 2008)的结果证实了这一点：我们的研究人员数量在2008年RAE中显示出正在进行世界领先的研究，使伦敦大学学院跻身世界顶尖大学之列。特别是，我将作为一个已建立的多学科团队的一员工作，该团队的任务是为患病或受损的头颈部组织提供新的治疗方法，这将使我能够利用世界上任何其他地区无与伦比的一系列专业知识和资源。

项目成果

Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine.

• DOI: 10.1002/sctm.16-0443
• 发表时间: 2017-06
• 期刊: Stem cells translational medicine
• 影响因子: 6
• 作者: Elliott MJ;Butler CR;Varanou-Jenkins A;Partington L;Carvalho C;Samuel E;Crowley C;Lange P;Hamilton NJ;Hynds RE;Ansari T;Sibbons P;Fierens A;McLaren C;Roebuck D;Wallis C;Muthialu N;Hewitt R;Crabbe D;Janes SM;De Coppi P;Lowdell MW;Birchall MA
• 通讯作者: Birchall MA

Co-culture-expanded human basal epithelial stem cells for application in tracheal tissue engineering

共培养扩增人基底上皮干细胞在气管组织工程中的应用

• 发表时间: 2016
• 期刊: LANCET
• 影响因子: 168.9
• 作者: Butler Colin R.

Use of a decellularised dermis scaffold and human bronchial epithelial cells to tissue engineer airway mucosa suitable for tracheal transplantation

使用脱细胞真皮支架和人支气管上皮细胞对适合气管移植的气道粘膜进行组织工程

• 发表时间: 2017
• 期刊: LANCET
• 影响因子: 168.9
• 作者: Hamilton Nicholas J. I.

Reply to: "Recent Advances in Circumferential Tracheal Replacement and Transplantation"

回复：《环型气管置换与移植的最新进展》

• DOI: 10.1111/ajt.13736
• 发表时间: 2016
• 期刊: American Journal of Transplantation
• 影响因子: 8.8
• 作者: Hamilton N

Use of a collagen I scaffold with embedded respiratory fibroblasts and Rho kinase inhibitor to tissue-engineer airway mucosa

使用嵌入呼吸道成纤维细胞和 Rho 激酶抑制剂的 I 型胶原蛋白支架对气道粘膜进行组织工程

• 发表时间: 2016
• 期刊: LANCET
• 影响因子: 168.9
• 作者: Hamilton Nick J.