Garcia-Alegria Eva, Iliut Maria, Stefanska Monika, Silva Claudio, Heeg Sebastian, Kimber Susan J, Kouskoff Valerie, Lacaud Georges, Vijayaraghavan Aravind, Batta Kiran
Cancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
School of Materials and National Graphene Institute, University of Manchester, UK.
Sci Rep. 2016 May 20;6:25917. doi: 10.1038/srep25917.
Pluripotent stem cells represent a promising source of differentiated tissue-specific stem and multipotent progenitor cells for regenerative medicine and drug testing. The realisation of this potential relies on the establishment of robust and reproducible protocols of differentiation. Several reports have highlighted the importance of biomaterials in assisting directed differentiation. Graphene oxide (GO) is a novel material that has attracted increasing interest in the field of biomedicine. In this study, we demonstrate that GO coated substrates significantly enhance the differentiation of mouse embryonic stem (ES) cells to both primitive and definitive haematopoietic cells. GO does not affect cell proliferation or survival of differentiated cells but rather enhances the transition of haemangioblasts to haemogenic endothelial cells, a key step during haematopoietic specification. Importantly, GO also improves, in addition to murine, human ES cell differentiation to blood cells. Taken together, our study reveals a positive role for GO in haematopoietic differentiation and suggests that further functionalization of GO could represent a valid strategy for the generation of large numbers of functional blood cells. Producing these cells would accelerate haematopoietic drug toxicity testing and treatment of patients with blood disorders or malignancies.
多能干细胞是再生医学和药物测试中分化的组织特异性干细胞和多能祖细胞的一个有前景的来源。这种潜力的实现依赖于建立稳健且可重复的分化方案。一些报告强调了生物材料在辅助定向分化中的重要性。氧化石墨烯(GO)是一种新型材料,在生物医学领域引起了越来越多的关注。在本研究中,我们证明了GO包被的基质显著增强了小鼠胚胎干细胞(ES细胞)向原始造血细胞和定型造血细胞的分化。GO不影响分化细胞的增殖或存活,而是增强了成血管细胞向造血内皮细胞的转变,这是造血特化过程中的关键步骤。重要的是,除了小鼠ES细胞外,GO还能改善人ES细胞向血细胞的分化。综上所述,我们的研究揭示了GO在造血分化中的积极作用,并表明GO的进一步功能化可能是生成大量功能性血细胞的有效策略。生产这些细胞将加速造血药物毒性测试以及对血液疾病或恶性肿瘤患者的治疗。