Graphene Oxide promotes embryonic stem cell differentiation to haematopoietic lineage

Abstract

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.

New insights into the regulation by RUNX1 and GFI1(s) proteins of the endothelial to hematopoietic transition generating primordial hematopoietic cells

“…In addition, it will be important to identify the components of the cellular niches that trigger and support the generation of the different types of blood cells by EHT in order to reproduce these processes in vitro to produce cell populations appropriate for clinical purposes 98-103 . Along this line, we recently demonstrated the relevance of a specific combination of cytokines, 104 heparin sulfates 105,106 and graphene oxide 107 in supporting the development of blood cells in vitro . Altogether the Gfi1 GFP knockin model represents a powerful tool to address in the future these outstanding questions and study the EHT process in more detail as the expression of Gfi1 in the endothelium can be used to accurately identify and purify hemogenic endothelium and cells undergoing EHT.…”

Toxicity studies of six types of carbon nanoparticles in a chicken-embryo model

“…The promotion of both primitive and definitive hematopoiesis by GO is consistent with the fact that primitive and definitive progenitors are generated from hemogenic endothelium precursors. 49 Our results indicate that rGO affects the shape and size of RBCs, which became more oval and generally smaller. However, we think that RBCs from the rGO group are immature forms of avian erythrocytes rather than indications of pathology, because they have irregular cytoplasmic polychromasia and a more rounded, pale nucleus.…”

The potential of nanoparticles in stem cell differentiation and further therapeutic applications

“…Recently, an interesting study demonstrated the capacity of GO to enhance the differentiation of ESCs into the hematopoietic progenitor cells . In this study, ESCs grown on GO‐coated culture substrates, showed remarkable ability to generate primitive and definitive hematopoietic cells that could be differentiated in vitro.…”