Manipulation of niche signals to advance cell therapies for liver disease
操纵生态位信号以推进肝病细胞疗法
基本信息
- 批准号:MR/L006537/1
- 负责人:
- 金额:$ 150.82万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Fellowship
- 财政年份:2014
- 资助国家:英国
- 起止时间:2014 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Liver disease is the fifth commonest cause of death in the UK and its incidence is rapidly increasing. Currently the only cure for liver failure is to replace the failing organ with a new one - a procedure known as a liver transplant. Unfortunately we simply do not have enough donor organs to meet the surging demands of patients requiring new livers.Over the last few years, a new technology named "induced pluripotency" (iPS) has emerged as a potential solution to this problem. In this technique skin cells obtained from a patient can be reprogrammed in a dish and then converted into liver cells before being transplanted back into the same patient. In this way it is believed that a full organ transplant could be avoided and in addition no harmful immuno-suppressant medications would be required.The first wave of induced pluripotent stem cell products, whilst promising, illustrated several problems. The main one being that cells produced in a dish did not appear mature enough to produce a cure if used in a patient. In fact, cells produced up till now look more like fetal or progenitor cells. Thus, in order to take these cells into clinical application, major advances to our current understanding that allow the final steps of maturation and subsequent transplantation to be successful will be needed. Many researchers believe that the niche ("the soil") surrounding cells ("the seed") has a profound effect upon their behaviour. Understanding the soil therefore may be the key to overcoming problems we have experienced with the seeds. By understanding how the niche influences both progenitor (baby) and adult liver cells in the developing, adult and diseased livers, I will be able to design new strategies to overcome such problems. My overall aim therefore is to use this new knowledge to develop cell based therapies for serious and otherwise untreatable liver diseases.
肝病是英国最常见的死亡原因,其发病率正在迅速增加。目前,唯一的肝衰竭治疗方法是用新的器官替换失败的器官 - 一种称为肝移植的过程。不幸的是,我们根本没有足够的供体器官来满足需要新肝脏的患者的激增需求。在过去的几年中,一种名为“诱导多能性”(IPS)的新技术已成为解决此问题的潜在解决方案。在此技术中,可以在菜肴中重新编程从患者获得的皮肤细胞,然后将其转换为肝细胞,然后再移植回同一患者。通过这种方式,人们相信可以避免进行完整的器官移植,此外,不需要有害的免疫抑制剂药物。诱导多能干细胞产物的第一波浪潮,同时有希望的,这说明了几个问题。主要的是,在菜肴中产生的细胞看起来不够成熟,无法在患者中使用治疗。实际上,到现在为止产生的细胞看起来更像是胎儿或祖细胞。因此,为了将这些细胞纳入临床应用,我们当前的理解允许允许成熟和随后的移植成功得出的重大进展。许多研究人员认为,周围细胞(“种子”)的利基(“土壤”)对其行为具有深远的影响。因此,了解土壤可能是克服种子遇到的问题的关键。通过了解开发,成年和患病肝脏中祖细胞(婴儿)和成年肝细胞的影响如何,我将能够设计新的策略来克服此类问题。因此,我的总体目的是利用这种新知识来开发基于细胞的疗法,以治疗严重或不可治疗的肝脏疾病。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
- DOI:10.1038/s41467-019-11266-x
- 发表时间:2019-07-26
- 期刊:
- 影响因子:16.6
- 作者:Segal, Joe M.;Kent, Deniz;Rashid, S. Tamir
- 通讯作者:Rashid, S. Tamir
Liver: Taking out the JuNK to treat a1-antitrypsin deficiency.
肝脏:取出JuNK来治疗α1-抗胰蛋白酶缺乏症。
- DOI:10.1038/nrgastro.2017.22
- 发表时间:2017
- 期刊:
- 影响因子:0
- 作者:Rashid ST
- 通讯作者:Rashid ST
Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency.
- DOI:10.1016/j.jhepr.2022.100446
- 发表时间:2022-04
- 期刊:
- 影响因子:0
- 作者:Li CZ;Ogawa H;Ng SS;Chen X;Kishimoto E;Sakabe K;Fukami A;Hu YC;Mayhew CN;Hellmann J;Miethke A;Tasnova NL;Blackford SJI;Tang ZM;Syanda AM;Ma L;Xiao F;Sambrotta M;Tavabie O;Soares F;Baker O;Danovi D;Hayashi H;Thompson RJ;Rashid ST;Asai A
- 通讯作者:Asai A
Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications.
- DOI:10.1016/j.stemcr.2018.01.025
- 发表时间:2018-03-13
- 期刊:
- 影响因子:5.9
- 作者:Ong J;Serra MP;Segal J;Cujba AM;Ng SS;Butler R;Millar V;Hatch S;Zimri S;Koike H;Chan K;Bonham A;Walk M;Voss T;Heaton N;Mitry R;Dhawan A;Ebner D;Danovi D;Nakauchi H;Rashid ST
- 通讯作者:Rashid ST
Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold.
- DOI:10.1016/j.biomaterials.2018.07.043
- 发表时间:2018-11
- 期刊:
- 影响因子:14
- 作者:Ng SS;Saeb-Parsy K;Blackford SJI;Segal JM;Serra MP;Horcas-Lopez M;No DY;Mastoridis S;Jassem W;Frank CW;Cho NJ;Nakauchi H;Glenn JS;Rashid ST
- 通讯作者:Rashid ST
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Tamir Rashid其他文献
Tight Junction Protein 2 (TJP2) regulates canalicular network formation and the polarity of human hepatocytes
紧密连接蛋白 2 (TJP2) 调节小管网络的形成和人肝细胞的极性
- DOI:
- 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
Eriko Kishimoto;Yuhi Hakozaki;Ashley Cast;Kari Huppert;Tamir Rashid;Richard Thompson;Masahiko Itoh;Hisamitsu Hayashi;Stacey Huppert;Akihiro Asai - 通讯作者:
Akihiro Asai
Tamir Rashid的其他文献
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{{ truncateString('Tamir Rashid', 18)}}的其他基金
Pluripotent stem cell derived hepatocytes for liver failure (PUSH for LIFE)
多能干细胞衍生的肝细胞治疗肝衰竭(PUSH for LIFE)
- 批准号:
MR/Z503940/1 - 财政年份:2024
- 资助金额:
$ 150.82万 - 项目类别:
Research Grant
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- 资助金额:20.0 万元
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