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TPO/SCF/Flt3L: 支持造血干/祖细胞（HSPC）体外生成与扩增重要因子
1385 人阅读发布时间：2024-09-20 16:30
造血干细胞（hematopoietic stem cell, HSPC）是一类成体组织干细胞，其功能定义是具有自我更新（即通过细胞分裂产生子代HSPC）和多能分化（即产生任何成熟的成人造血细胞类型）潜力的细胞。因其独特的生物学特性，目前HSPC的应用被分为两个方向：一是利用HSPC的自我更新、运动迁移等能力，用干细胞进行回输治疗而发展出的干细胞移植技术和干细胞基因治疗，目前这两种技术已被用于治疗血液系统良恶性疾病、实体肿瘤（如视神经母细胞瘤）、Fanconi贫血等多种疾病。二是由于HSPC可通过定向分化产生淋巴系和髓系等造血祖细胞，进而大量增殖分化成各类成熟的功能性细胞，常作为诱导多能性干细胞（iPSC）向免疫细胞分化的主要中间阶段之一。
Fig1. The haematopoietic hierarchy and genetic disorders
无论是造血干细胞移植技术的应用还是干细胞基因疗法的临床转化或是作为干细胞向效应细胞分化的中间阶段之一，都亟需解决HSPC扩增这一根本性问题。目前，用于干细胞扩增的技术和方法层出不穷，通过添加细胞因子、小分子化合物和模拟HSPC生存环境以及基因编辑干预进行HSPC体外培养扩增，进而实现HSPC的数量增加满足临床需求。
Fig2. Components of ex vivo HSPC culture systems
作为HSPC体外扩增优化策略之一，上世纪90年代首次报道了使用不同细胞因子组合扩增HSPC的方法。Takahiro等测试了单一细胞因子和细胞因子组合培养的HSPC细胞的长期再生能力。结果显示，在这些细胞因子中，干细胞因子（stem cell factor，SCF）、酪氨酸激酶3配体（fms-related tyrosine kinase 3 ligand，FLT3-L）和血小板生成素（thrombopoietin，TPO）以及IL-6和可溶性IL-6受体复合物（IL-6/sIL-6R）的组合形式：SCF+FL+TPO+IL-6/sIL-6R是使细胞扩增倍数最多、干细胞标志物CD45表达量最高的方式，这种因子组合也是目前公认在HSPC早期阶段起诱导自我更新和促进体外扩增的常见扩增培养策略。
Fig3. 细胞因子组合培养策略
为解决HSPC体外培养扩增等相关问题，减少HSPC体外扩增时间、提升HSPC扩增效率，ACROBiosystems百普赛斯开发了一系列用于HSPC体外培养扩增的GMP级TPO、SCF、Flt3L、IL-3、IL-6等相关产品，产品性能均经过实验验证，现货发售！更有限时试用装活动来袭，快来选购吧！
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SCF&TPO&FLT3L等因子高效促进iPSCs向HSPC的分化
GMP Grade SCF(GMP-SCFH25), TPO(GMP-THNH25), FLT3L(GMP-FLLH28), FGF basic (GMP-FGCH17) and VEGF165 (GMP-VE5H23) could significantly promote the iPSC differentiation to HSPCs after 14 days, highly expressed hematopoietic stem cell markers CD34 and CD45.
Cellular morphology during HSPC differentiation. Embryoid bodies were formed with iPSCs in mTeSR-plus at Day 0-1. Then HSPC differentiation was carried out with BMP4, VEGF, FGF2, SCF, TPO, Flt3L and other factors in StemPro®-34 SFM Complete Medium for another 13 days. At Day 14, HSPCs were collected from both suspension cells and remaining embryoid bodies. Scale bar, 500 μm
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SCF&TPO&FLT3L等因子支持HSPC体外快速扩增
GMP Grade TPO (GMP-THNH25) is crucial for the expansion of human CD34+ hematopoietic cells cultured with medium containing GMP Grade SCF (GMP-SCFH25) and Flt-3 Ligand (GMP-FLLH28). The cell viability was checked with a luminescent cell viability detection reagent.
GMP Grade SCF (GMP-SCFH25), FLT3L (GMP-FLLH28), IL-3 (GMP-L03H18) and IL-6 (GMP-L06H27) could support the rapid cell expansion and good cell viability of CD34+ hematopoietic stem cells.
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货号 |
产品描述 |
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GMP-THNH25 |
GMP Human Thrombopoietin Protein |
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GMP-SCFH25 |
GMP Human SCF Protein |
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GMP-FLLH28 |
GMP Human Flt-3 Ligand Protein |
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GMP-L03H18 |
GMP Human IL-3 Protein |
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GMP-L06H27 |
GMP Human IL-6 Protein |
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GMP-FGCH17 |
GMP Human FGF basic Protein |
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GMP-VE5H23 |
GMP Human VEGF165 Protein |
参考文献
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5.Ferrari, Giuliana et al. “Gene therapy using haematopoietic stem and progenitor cells.” Nature reviews. Genetics vol. 22,4 (2021): 216-234. doi:10.1038/s41576-020-00298-5
6.Arias, Jonathan et al. “Hematopoietic stem cell- and induced pluripotent stem cell-derived CAR-NK cells as reliable cell-based therapy solutions.” Stem cells translational medicine vol. 10,7 (2021): 987-995. doi:10.1002/sctm.20-0459