Human blood stem cell expansion: Empowering new technology for stem cell medicine

人类血液干细胞扩增：为干细胞医学提供新技术

• 批准号: MR/V005502/1
• 负责人: David Kent
• 金额: $ 80.9万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV005502%2F1
• 关键词: Human; blood; stem; cell; expansion

Blood stem cells are the fundamental component of regenerative medicine applications involving the blood and immune system, including bone marrow transplantation and gene therapy applications. Despite significant efforts and investment, researchers have largely failed to maintain fully functional blood stem cells for substantial periods of time outside the body. As a result, the limiting factor for cell and gene therapies is often obtaining a sufficient number of blood stem cells to seed the production of mature cells in vitro (e.g., red blood cells, platelets) or to lead to successful longterm bone marrow transplantation (e.g., gene therapy).Our recent advances in mouse blood stem cell expansion put us on the cusp of breaking through a decades-old barrier and this novel cell expansion system urgently requires characterisation and translation to human HSCs. Our proposal brings together leading UK and Japanese researchers in the molecular and functional characterisation of mouse and human blood stem cells in order to leverage their complementary expertise to translate this technology to the human system and explore potential clinical applications.

造血干细胞是涉及血液和免疫系统的再生医学应用的基本组成部分，包括骨髓移植和基因治疗应用。尽管付出了巨大的努力和投资，但研究人员在很大程度上未能在体外长时间维持功能齐全的造血干细胞。因此，细胞和基因疗法的限制因素通常是获得足够数量的造血干细胞以在体外接种成熟细胞的产生（例如，红细胞，血小板）或导致成功的长期骨髓移植（例如，我们在小鼠血液干细胞扩增方面的最新进展使我们处于突破数十年屏障的尖端，并且这种新型细胞扩增系统迫切需要表征和转化为人HSC。我们的提案汇集了英国和日本在小鼠和人类血液干细胞的分子和功能表征方面的领先研究人员，以利用他们互补的专业知识将这项技术转化为人类系统并探索潜在的临床应用。

项目成果

A highly efficient reporter system for identifying and characterizing in vitro expanded hematopoietic stem cells

• DOI: 10.1101/2021.06.18.448972
• 发表时间: 2021-06
• 期刊: bioRxiv
• 作者: J. Che;D. Bode;I. Kucinski;A. Cull;Fiona Bain;Melania Barile;Grace Boyd;M. Belmonte;M. Jassinskaj

Resolving the hematopoietic stem cell state by linking functional and molecular assays.

• DOI: 10.1182/blood.2022017864
• 发表时间: 2023-08-10
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Jassinskaja, Maria;Gonka, Monika;Kent, David G.
• 通讯作者: Kent, David G.

Hematopoietic stem cells depend on HIM and HER.

造血干细胞依赖于 HIM 和 HER。

• DOI: 10.1016/j.exphem.2022.10.004
• 发表时间: 2022
• 期刊: Experimental hematology
• 影响因子: 2.6
• 作者: Kent DG

Exploiting Single-Cell Tools in Gene and Cell Therapy.

• DOI: 10.3389/fimmu.2021.702636
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Bode D;Cull AH;Rubio-Lara JA;Kent DG
• 通讯作者: Kent DG

Lessons from early life: understanding development to expand stem cells and treat cancers.

• DOI: 10.1242/dev.201070
• 发表时间: 2022-10-15
• 期刊: Development (Cambridge, England)