Planting the Seed

Planting the Seed

By: James LeFevre and Neha Majety

Embryonic stem cell treatment is a promising method of treating and potentially curing type 1 diabetes (T1D). Embryonic stem cells are pluripotent with infinite proliferative capacity and self-renewal. These features make them highly desirable as way of reinstating insulin production in T1D. Consequently, understanding embryonic growth and development is imperative. Like an embryo, our research too, must grow and develop to expedite the cure for T1D. 

Shining a Light on the “Black Box”

Prior to gastrulation, investigating embryonic development in the implantation stage is difficult due to limited accessibility and ethical dilemmas. Gu and colleagues call this period a “black box”, alluding to its largely unclear process. 

Fortunately, some nearby bifocal glasses may provide a clearer picture. In one lens, the top-down approach uses natural embryos as the focal point of manipulation and observation for understanding embryonic development. In the other lens, an embryo model created by bottom-up stem cell self-assembly is used to study early embryonic development through better experimental design visualization. 

Gu and colleagues also discuss bioengineering microenvironments for early embryo culture. That is, through different in vitro culture platforms, their geometry and mechanics, and biomaterials. Biomaterials, specifically, are crucial for early embryo culture. The nature of biomaterials influence embryonic development through mechanical support and physicochemical signals.

Modeling Our Way into the Future

The Xiang team reported on a method to successfully culture human blastocysts and recreate a post-implantation early human embryo system. Specifically, they described a 3D blastocyst-culture system that was found to display nearly all human embryo developmental landmarks. Through this model they were able to examine embryonic development for many lineage markers including epiblast (EPI) and trophoblast (TrB) populations. Overall, they identified unique developmental features of the early human embryo providing a greater understanding of stem cell pluripotency and informing stem cell processes such as differentiation and renewal.

More recently, another group of researchers designed and implemented a microfluidic device tasked to model early human embryo development. The device was created from human pluripotent stem cells (hPSCs). In past models like the Gel-3D model, these cells, when cultured, formed clusters that mainly differentiated uniformly; however, there was a small minority that differentiated asymmetrically. This minority is key to modeling the early developing embryo since the population is characteristic of the early human embryo and with further development it is shown to depict known human embryo development landmarks. However, as stated prior, this population in such models is a minority and thus inefficient. This is where the microfluidic device comes into the picture as it addresses the issue of inefficiency. 

What is the role of microfluidics in this device? In a dynamic and complex system like the early developing embryo, it is essential that researchers can exert some sort of control on the system to better experiment with and understand the system. Microfluidics create tiny channels that allow for the precision necessary to control the location and preliminary cell count in a system like the human embryo, generate signals that can lead to controlled self-organization, and are compatible with many fluorescence imaging methods.  

The device provides researchers with a method by which to side-step the ethical issues associated with embryonic research while increasing efficiency and control. Though the device itself cannot recreate the entire human embryo, as it was never intended to do so, it does allow the early human embryonic development stages to be more easily accessed and more thoroughly studied.

Putting it all together

The promising outlook of embryonic stem cell treatments demand for new or improved methods of research to overcome the adversities of ethics and inaccessibility. As discussed, novel 3D culture systems or microfluidic devices may serve as useful tools for advancing research. Hopefully, these advancements, and others to come, lead to safe and effective treatments for T1D.

Sources

• Gu, Z., Guo, J., Wang, H., Wen, Y., & Gu, Q. (2020). Bioengineered microenvironment to culture early embryos. Cell Proliferation, 53(2). https://doi.org/10.1111/cpr.12754 
• Xiang, L., Yin, Y., Zheng, Y., Ma, Y., Li, Y., Zhao, Z., … Li, T. (2019). A developmental landscape of 3D-cultured human pre-gastrulation embryos. Nature, 577(7791), 537–542. https://doi.org/10.1038/s41586-019-1875-y 
• Zheng, Y., Shao, Y., & Fu, J. (2020). A microfluidics-based stem cell model of early post-implantation human development. Nature Protocols, 16(1), 309–326. https://doi.org/10.1038/s41596-020-00417-w