美国华盛顿大学Colleen Delaney和Shaoyi Jiang等研究人员合作研发了可用于扩增原代人造血干细胞的两性水凝胶。该研究于2019年10月7日在线发表在《自然—医学》上。
通过在可降解的两性离子水凝胶中使用人类造血干细胞和祖细胞（HSPC）的3D培养，研究人员实现了对CD34阳性脐带血和骨髓来源的HSPC进行保持原始状态的显著扩增。这种培养系统使得长期造血干细胞（LT-HSC）频率增加了73倍，这是通过有限稀释测定法证明的，并且扩增的HSPC能够在免疫受损的小鼠中造血至少24周。水凝胶的两性离子特性和3D形式对于HSPC自我更新都很重要。从机理上讲，3D两性离子水凝胶培养对减少HSPC分化和促进自我更新的影响可能是通过抑制O2相关代谢来抑制过量的活性氧（ROS）产生所实现的。因此，使用两性离子水凝胶进行HSPC扩增具有促进造血干细胞疗法临床应用的潜力。
据悉，离体扩增HSPC的能力对于完全实现基于HSPC的疗法的潜力至关重要。特别是由于HSPC有限的可用性阻碍了临床有效疗法的应用，例如脐带血移植。
附：英文原文
Title: Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel
Author: Tao Bai, Jianqiang Li, Andrew Sinclair, Suzan Imren, Fabiola Merriam, Fang Sun, Mary Beth OKelly, Cynthia Nourigat, Priyesh Jain, Jeffrey J. Delrow, Ryan S. Basom, Hsiang-Chieh Hung, Peng Zhang, Bowen Li, Shelly Heimfeld, Shaoyi Jiang, Colleen Delaney
Issue&Volume: 2019-10-07
Abstract: The ability to expand hematopoietic stem and progenitor cells (HSPCs) ex vivo is critical to fully realize the potential of HSPC-based therapies. In particular, the application of clinically effective therapies, such as cord blood transplantation, has been impeded because of limited HSPC availability. Here, using 3D culture of human HSPCs in a degradable zwitterionic hydrogel, we achieved substantial expansion of phenotypically primitive CD34+ cord blood and bone-marrow-derived HSPCs. This culture system led to a 73-fold increase in long-term hematopoietic stem cell (LT-HSC) frequency, as demonstrated by limiting dilution assays, and the expanded HSPCs were capable of hematopoietic reconstitution for at least 24 weeks in immunocompromised mice. Both the zwitterionic characteristics of the hydrogel and the 3D format were important for HSPC self-renewal. Mechanistically, the impact of 3D zwitterionic hydrogel culture on mitigating HSPC differentiation and promoting self-renewal might result from an inhibition of excessive reactive oxygen species (ROS) production via suppression of O2-related metabolism. HSPC expansion using zwitterionic hydrogels has the potential to facilitate the clinical application of hematopoietic-stem-cell therapies. Expansion of human hematopoietic stem cells present in cord blood or bone marrow can be achieved by cell culture in a hydrogel, potentially facilitating clinical applications of hematopoietic cell transplantation.
DOI: 10.1038/s41591-019-0601-5
Source:https://www.nature.com/articles/s41591-019-0601-5
Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex
本期文章：《自然—医学》：Online/在线发表
