Department of Hematology, Singapore General Hospital, Singapore; Department of Pharmacy, National University of Singapore, Singapore.
Nanomedicine. 2013 Nov;9(8):1304-16. doi: 10.1016/j.nano.2013.05.009. Epub 2013 Jun 1.
In this study, carboxylic acid functionalized single walled carbon nanotubes (f-SWCNT-COOH) was shown to support the viability and ex vivo expansion of freeze-thawed, non-enriched hematopoietic stem and progenitor cells (HSPC) in human umbilical cord blood-mononucleated cells (UCB-MNC). Our in vitro experiments showed that f-SWCNT-COOH increased the viability of the CD45(+) cells even without cytokine stimulation. It also reduced mitochondrial superoxides and caspase activity in CD45(+) cells. f-SWCNT-COOH drastically reduced the proportions of CD45(-) cells in the non-enriched UCB-MNC. Phenotypic expression analysis and functional colony forming units (CFU) showed significant ex vivo expansion of HSPC, particularly of CD45(+)CD34(+)CD38(-) population and granulocyte-macrophage (GM) colonies, in f-SWCNT-COOH augmented cultures supplemented with basal cytokines. In vivo data suggested that f-SWCNT-COOH expanded UCB-MNC could repopulate immunodeficient mice models with minimal acute or sub-acute symptoms of graft-versus-host disease (GVHD) and f-SWCNT-COOH dependent toxicity.
In this paper a novel method is presented by using single wall functionalized carbon nanotubes to enhance viability and ex vivo expansion of freeze-thawed, non-enriched hematopoietic stem and progenitor cells in human umbilical cord blood -mononucleated cells. Detailed data is presented about enhanced viability, including improved repopulation of immunodeficient mice models with minimal acute or sub-acute symptoms of graft-versus-host disease.
在这项研究中,羧酸功能化单壁碳纳米管(f-SWCNT-COOH)被证明能够支持冷冻解冻的、非富集的造血干细胞和祖细胞(HSPC)在人脐血单核细胞(UCB-MNC)中的活力和体外扩增。我们的体外实验表明,即使没有细胞因子刺激,f-SWCNT-COOH 也能提高 CD45(+)细胞的活力。它还降低了 CD45(+)细胞中的线粒体超氧化物和半胱天冬酶活性。f-SWCNT-COOH 大大降低了非富集 UCB-MNC 中 CD45(-)细胞的比例。表型表达分析和功能性集落形成单位(CFU)显示,HSPC,特别是 CD45(+)CD34(+)CD38(-)群体和粒细胞-巨噬细胞(GM)集落,在 f-SWCNT-COOH 增强的培养物中得到了显著的体外扩增,这些培养物补充了基础细胞因子。体内数据表明,f-SWCNT-COOH 扩增的 UCB-MNC 可以重新填充免疫缺陷小鼠模型,而急性或亚急性移植物抗宿主病(GVHD)和 f-SWCNT-COOH 依赖性毒性的症状最小。
本文提出了一种新的方法,即用单壁功能化碳纳米管来增强冷冻解冻的、非富集的造血干细胞和祖细胞在人脐血单核细胞中的活力和体外扩增。详细的数据显示了增强的活力,包括最小化急性或亚急性移植物抗宿主病症状的免疫缺陷小鼠模型的重新填充。