RegenVOX: phase I/II clinical trial of stem cell based tissue engineered laryngeal implants

喉在吞咽过程中保护气道，调节呼吸，并允许声音：所有基本的人类功能。每年有超过2000名英国患者因创伤或癌症而失去喉功能，需要在医院或在医院度过大量时间。每年有1300名NHS患者的喉部被完全切除。对这些患者的常规治疗使许多人在说话、吞咽和呼吸方面存在严重问题。例如，使用联合化疗和放疗治疗喉癌会导致声音嘶哑和吞咽疼痛，甚至会使喉部完全残疾。然而，如果我们能够准确地替换喉部的正常轮廓和结构，例如通过使用活组织工程替代物，这些患者的生活质量（以及某些情况下的生存率）将得到改善。在这个项目中，我们建立在一些广为人知的成功取代成人和儿童的气管，提供由患者自己的干细胞和喉支架制备的喉重建产品，并获得适当的许可，从移植供体。因此，我们的目标是生产一种安全，有效和合理的治疗适合常规NHS使用，从而提高患者和护理人员的生活质量。该产品将是一种部分喉替代结构，由一个人供体支架组成，所有供体细胞都已被化学剥离。这意味着植入物不会像正常移植一样被排斥，因此患者不需要免疫抑制剂药物，也不需要所有的副作用。基于广泛的实验室工作，我们能够将患者的干细胞转化为软骨细胞，为产品提供天然强度，并产生替代粘膜，就像正常的喉一样。类似的技术在我们的成人和儿童气管接受者中效果很好，他们接受气管治疗是为了挽救生命。为了完成这项工作，我们还需要为临床试验做几年的准备，然后将对10名植入患者进行两年的随访，以向监管机构证明该产品是安全有效的。反过来，这将使我们能够申请在NHS中常规使用该技术，并将其推向市场，为我们的医院带来急需的资金。由于这是第一个基于干细胞的器官替代进入临床试验，据我们所知，该项目对其他相关器官替代（如食管和肺）具有深远的“寻路”意义。通过开发在这样的试验中研究人体细胞和组织的方法，我们将从这项工作中获得更多的价值，这样我们就可以尽可能多地了解干细胞和组织修复的基础科学。最后，我们将研究将这样的治疗方法转移到常规医疗保健中的详细经济学，并确定最具成本效益的方法，并确保任何新发明都能为英国带来尽可能多的资金。

The larynx protects the airway during swallowing, regulates breathing, and permits voice: all fundamental human functions. Over 2000 UK patients lose laryngeal function due to trauma or cancer annually and need to spend a lot of time at or in hospitals. 1300 NHS patients a year have their larynx removed entirely. Conventional treatments for these patients leave many with substantial problems talking, swallowing and breathing. For example, the use of combined chemotherapy and radiotherapy for laryngeal cancer results in hoarseness and painful swallowing and can even render the larynx completely disabled. However, if we could accurately replace the normal contours and structure of the larynx, for example by using a living tissue-engineered replacement, the quality of life (and in some cases survival) of these patients would be transformed. In this project we build on some well-publicised successes in replacing the windpipes of adults and children to deliver a laryngeal reconstruction product made from the patient's own stem cells and a laryngeal scaffold prepared, with appropriate permissions, from transplant donors. Our goal is thereby to produce a safe, effective and reasonably therapy suitable for routine NHS use, resulting in improved quality of life for patients and carers. The product will be a partial laryngeal replacement construct, composed of a a human donor scaffold from which all donor cells have been chemically stripped. This means that the implant will not get rejected, like normal transplants, and so patients do not need immunosuppressant medication, with all the side effects that would entail. Based on extensive laboratory work, we are able to turn the patient's stem cells into cartilage-producing cells to give natural strength to the product, and also produce a replacement mucous membrane to line the inside, just like a normal larynx. Similar technology worked well for our adult and child windpipe recipients treated for life-saving reasons. To perform this work, we need a further years' preparation for a clinical trial, which will then follow ten implanted patients for two years in order to demonstrate to the regulatory authorities that the product is both safe and effective. This will, in turn, allow us to apply to use the technology routinely in the NHS and to market it to bring in much needed funds to our hospitals. Since this is the first stem-cell based organ replacement to enter clinical trials to our knowledge, this project has far-reaching 'path-finding' implications for other related organ replacements such as those for oesophagus and lung. Even more value will be obtained from this work by developing ways of studying cells and tissues in man in trials like this so that we can learn as much about the underlying science of stem cells and tissue repair as possible. Finally, we will study the detailed economics of moving treatments like this into routine healthcare, and determine the most cost-effective ways this can be managed, as well as making sure that any new inventions bring in as much finance as possible to the UK.