Department of Neuroscience, Karolinska Institutet, Stockholm 171 77, Sweden.
IFM, Department of Chemistry, Linköping University, Linköping 581 83, Sweden.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3790-3797. doi: 10.1021/acsabm.3c00447. Epub 2023 Aug 30.
There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease, such as in brain tumors, due to the potential clinical importance in prognosis, diagnosis, and treatment of diseases of the nervous system. Here, we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) stem cell-like cells and NSPCs. While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSPCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same cell population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of neural and glioma stem and progenitor cells.
由于在神经系统疾病的预后、诊断和治疗方面具有潜在的临床重要性，因此迫切需要一种简单、非侵入性的方法来识别发育中和成年大脑中的活神经干细胞/祖细胞（NSPC），以及在疾病中，如脑肿瘤。在这里，我们报告了一种发光共轭寡聚噻吩（LCO），名为 p-HTMI，可用于非侵入性和非扩增实时检测活的人源胶质母细胞瘤（GBM）干细胞样细胞和 NSPC。虽然 p-HTMI 仅染色了所研究的其他细胞类型的一小部分，但只需将 p-HTMI 添加到细胞培养物中，就可以在数分钟内有效检测来自啮齿动物和人类的 NSPC 或 GBM 细胞。p-HTMI 上功能化有一个甲基咪唑部分，类似于组氨酸/组胺的侧链，而非甲基化类似物则没有功能。人 GBM 细胞的分选实验表明，p-HTMI 标记的细胞群与 CD271 相同，CD271 是神经干细胞样细胞和胶质母细胞瘤中快速迁移细胞的一个建议标志物。我们的结果表明，LCO p-HTMI 是一种通用工具，可用于即时和选择性检测神经和神经胶质瘤干细胞和祖细胞。
