Epidermal Growth Factor and Three-dimensional Scaffolds Influencing the Differentiation of Mouse Embryonic Stem Cells

In a study done by researchers at School of Medicine, Shiraz University of Medical Sciences, a scaffold-based 3D co-culture system, using purified alginate was applied to induce oocyte differentiation from mouse embryonic stem cells (mESCs).

Embryonic stem cells (ESCs) have the capacity to generate all cell lineages of the body. They are ideal candidates to be differentiated into female and male germ cells in vitro. To generate female gametes in vitro, it is important to improve the efficiency of the induced germ cells.

Three-dimensional (3D) culture provides a biomimicry of the naive microenvironment that can support cell proliferation, differentiation and regeneration. Some growth factors, such as epidermal growth factor (EGF), facilitate normal meiosis during oocyte maturation in vivo.

In this study, mouse embryonic stem cells were induced to differentiate into oocyte-like cells using embryoid body (EB) protocol in the two-dimensional (2D) or 3D microenvironment in-vitro. The results revealed that germ cell differentiation significantly increased by EGF exposure in alginate-based 3D culture.

As a result, the cultures exposed to EGF in the alginate-based 3D microenvironment, showed the highest level of premeiotic, meiotic and oocyte maturation marker genes in comparison to other groups. According to the gene expression patterns, Iranian researchers concluded that alginate-based 3D co-culture system provided a highly efficient protocol for oocyte-like cell differentiation from mESCs. The obtained data demonstrated that this culture system along with EGF, improved the rate of in vitro oocyte-like cell differentiation.

The results of the aforementioned study indicated that this applied system could mimic the ovarian niche, which is superior to the conventional 2D system. Also the data highlights the importance of tissue engineering approach in differentiation of ESCs to oocyte-like cells, and supplementation of EGF is effective in improving the differentiation process.

However, further research is warranted for successful in vitro differentiation of ESCs to functional oocytes as a new form of infertility treatment.