Immunogenicity test platform - in vitro and in vivo

免疫原性测试平台 - 体外和体内

• 批准号: MR/S020934/1
• 负责人: Giovanna Lombardi
• 金额: $ 124.7万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS020934%2F1
• 关键词: Immunogenicity; test; platform; vitro; vivo

Regenerative medicine is a branch of medicine that aims to replace damaged or diseased tissue, thereby treating and potentially curing illnesses that are currently untreatable. Two different regenerative medicine approaches are currently being investigated: the first is to stimulate the body's own cells to repair the tissue; the second is to transplant new cells into the body. This research proposal focuses on the second approach, and in particular on the therapeutic potential of pluripotent stem cells. Pluripotent stem cells (or PSCs for short) are "master cells" capable of becoming any cell or tissue. They are also able to self-renew, meaning that they have the ability to produce endless copies of themselves. PSCs come in two types - embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs come from very early preimplantation embryos, whereas iPSCs are made by forcing adult cells back into a pluripotent state by using fairly recently developed technology known as cell reprogramming. Just like ESCs, iPSCs can expand indefinitely and can be used to make any tissue.Although there has been a huge amount of progress in making different types of human tissue from ESCs and iPSCs there are still lots of unanswered questions. In particular it is not known if cell and tissue products derived from ESCs and iPSCs will be rejected by the patient's immune system, in the same way that solid organs (like kidney and liver) are rejected if the recipient and donor are not "well matched". Our research aims to help address that question. Through a combination of laboratory experiments and animal (mouse) studies we will determine whether or not two cell products (ESC derived nerve cells and iPSC-derived liver cells) are capable of activating the human immune system. We have chosen these particular cell products as both are about to be tested in clinical trials involving patients with Parkinson's disease and liver failure.We believe that this study is important. As well as providing information on two specific clinical products - our project aims to establish a generic protocol for testing future cellular therapies and in doing so has the potential to significantly advance the field of regenerative cellular therapy.

再生医学是医学的一个分支，旨在替换受损或患病的组织，从而治疗并有可能治愈目前无法治愈的疾病。目前正在研究两种不同的再生医学方法：第一种是刺激人体自身细胞修复组织；第二种是将新细胞移植到体内。这项研究建议将重点放在第二种方法上，特别是多能干细胞的治疗潜力。多能干细胞(简称PSCs)是能够成为任何细胞或组织的“母细胞”。它们还能够自我更新，这意味着它们有能力制造无穷无尽的自我副本。PSCs有两种类型--胚胎干细胞(ESCs)和诱导多能干细胞(IPSCs)。ESCs来自非常早期的植入前胚胎，而IPSCs是通过使用最近发展的称为细胞重新编程的技术迫使成年细胞回到多能性状态而产生的。就像ESCs一样，IPSCs可以无限扩张，可以用来制造任何组织。尽管在从ESCs和IPSCs制造不同类型的人类组织方面已经取得了巨大的进展，但仍然有许多悬而未决的问题。特别是，目前尚不清楚来自ESCs和IPSCs的细胞和组织产品是否会被患者的免疫系统排斥，就像如果受者和捐赠者不“很匹配”，实体器官(如肾脏和肝脏)被排斥一样。我们的研究旨在帮助解决这个问题。通过实验室实验和动物(小鼠)研究相结合，我们将确定两种细胞产品(ESC来源的神经细胞和IPSC来源的肝细胞)是否能够激活人类免疫系统。我们选择了这些特殊的细胞产品，因为这两种产品都即将在涉及帕金森氏病和肝功能衰竭患者的临床试验中进行测试。我们相信这项研究很重要。除了提供两种特定临床产品的信息外，我们的项目还旨在建立测试未来细胞疗法的通用方案，这样做有可能显著推动再生细胞疗法领域的发展。

项目成果

Pluripotent Stem Cell-Derived Hepatocytes Inhibit T Cell Proliferation In Vitro through Tryptophan Starvation.

• DOI: 10.3390/cells11010024
• 发表时间: 2021-12-22
• 期刊: Cells
• 影响因子: 6
• 作者: Romano M;Elgueta R;McCluskey D;Ortega-Prieto AM;Stolarczyk E;Dazzi F;Lucendo-Villarin B;Meseguer-Ripolles J;Williams J;Fanelli G;Hay DC;Watt FM;Lombardi G
• 通讯作者: Lombardi G

The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cells in vitro: implications for the STEM-PD clinical trial.

RC17 hESC 衍生的多巴胺能神经祖细胞的体外免疫学特征：对 STEM-PD 临床试验的影响。

• DOI: 10.1101/2024.01.23.576826
• 发表时间: 2024
• 作者: Curle A

Immunological considerations and challenges for regenerative cellular therapies

再生细胞疗法的免疫学考虑和挑战

• DOI: 10.17863/cam.71858
• 发表时间: 2021
• 作者: Petrus-Reurer S

Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

在阿尔茨海默氏症和帕金森氏病中建模神经免疫系统。

• DOI: 10.1186/s12974-024-03024-8
• 发表时间: 2024-01-23
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3

Immunological considerations and challenges for regenerative cellular therapies.

• DOI: 10.1038/s42003-021-02237-4
• 发表时间: 2021-06-25
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Petrus-Reurer S;Romano M;Howlett S;Jones JL;Lombardi G;Saeb-Parsy K
• 通讯作者: Saeb-Parsy K