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Nov 4, 2015 | By Kira

In a paper published today, scientists reveal a new 3D bioprinting method for producing highly uniform ‘blocks’ of embryonic stem cells (ESCs), which have the capacity to differentiate into any cell type in the body. These blocks could be used as ‘lego bricks’ to build large-scale tissue structures for stem cell regulation and expansion, regenerative medicine, drug screening studies, and potentially even for the construction of micro-organs.

The study, carried out by researchers at Tsinghua University in Beijing and Drexel University in Philidelphia, represents the first time ESCs have been 3D printed into a 3D cell-laden hydrogel construct, producing uniform, pluripotent (able to generate almost any cell in the body), high-throughput and size-controllable embryoid bodies, with a 90% survival rate.

“It was really exciting to see that we could grow embryoid body in such a controlled manner,” said Wei Sun, a lead author on the paper. “The grown embryoid body is uniform and homogenous, and serves as a much better starting point for further tissue growth.”

In the paper, the researchers explain that because of their capacity for self-renewal and differentiation into nearly all cell types, ESCs hold great promise as an in vitro model system for studies in early embryonic development, and are also an important source for applications in diagnostics, therapeutics, and drug screening. However, previous methods for printing these cells, either via 2D creation in a petri-dish, or via a ‘suspension’ method, resulted in non-uniform ESCs. They found that reconstructing a 3D cell micro-environment, much like that found in vivo, would be critical to directing stem cell fate and generating uniform cell sources with high levels of proliferation for tissue engineering and other biomedical applications.

How Embryonic Stem Cell cultures can be used for medical purposes, via APBI Schools

Luckily, recent advances in bioprinting technologies allowed them to control the precise deposition of ESCs in a reproducible manner. They used a temperature-sensitive extrusion-based 3D bioprinter, previously developed in their lab for bioprinting hepatocytes and other complex cells, to produce a grid-like 3D structure that could grow embryoid bodies. These bodies could successfully self-renew for seven days while maintaining high pluripotency. Furthermore, about 90% of the bioprinted ESCs remained alive. The researchers believe that their 3D bioprinting technique could be used to develop embryoid bodies at a high throughput. They could then be used to by researchers to perform experiments on tissue regeneration and for drug screening studies.

Schematic representation of this research.

Images of the printed cellular model with grid structure. (A) Full view of the cellular construct. (B) Phase-contrast images demonstrating the cell morphology and distribution of different cell density at day 3, day 5 and day 7. Scale bar: 1 mm.

“Our next step is to find out more about how we can vary the size of the embryoid body by changing the printing and structural parameters, and how varying the embryoid body size leads to ‘manufacture’ of different cell types" said Rui Yao, another author on the paper. "In the longer term, we'd like to produce controlled heterogeneous embryonic bodies" said Wei Sun. "This would promote different cell types developing next to each other - which would lead the way for growing micro-organs from scratch within the lab."

The free article, titled Three-dimensional bioprinting of embryonic stem cells directs highly uniform embryoid body formation, was published today in the journal Biofabrication as part of their Special Issue on 3D Cell Printing. In addition to Wei Sun and Rui Yao, the authors are  Liliang Ouyang, Shuangshuang Mao and Xi Chen.

 

 

Posted in 3D Printing Application

 

 

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