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Bioprinting Stem Cells – A Viable Strategy to Create Transplantable Organs?

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Review of “Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D” from Biofabrication by Stuart P. Atkinson

It all started with Johannes Gutenberg and his famous press, but as the technology has moved on, our printing abilities seem only limited by our imaginations (or lack thereof!). So advanced is the technology, that we are now aiming to print three-dimensional (3D) tissue constructs. This version of printing, called bioprinting, aims to use stem cells or stem cell derivatives as the “ink” to form complex 3D cellular structures for use in disease modeling, drug testing, and ultimately, organ transplants.

One important consideration for the future success of bioprinting is the unavoidable stress that the cells endure during the process, stress which could affect survival, function, and differentiation potential. Now researchers from the laboratory of Wenmiao Shu (Heriot-Watt University, Edinburgh, Scotland) have studied the effects of valve-based bioprinting on human pluripotent stem cell (hPSCs) and cells undergoing differentiation towards hepatocyte-like cells (HLCs), and also investigated the potential for the construction of 3D liver organ structures [1].

Their exciting new study, using an improved cell-printing platform [2], found that by optimizing nozzle length and pressure settings, cells could survive the bioprinting process. 2D bioprinting of human stem cells (both embryonic and induced pluripotent) did not change their viability or pluripotency. Furthermore, bioprinting stem cells during their directed differentiation to HLCs [3] did not affect the ongoing differentiation process and generated 2D cultures of cells with the proper morphology and the ability to secrete albumin (like normal liver cells).

The success in 2D motivated the researchers to attempt the 3D construction of stem cells into an organ-like structure. To do this, the group bioprinting cells undergoing differentiation within a 3D alginate hydrogel matrix. Alginate hydrogels are biocompatible, non-immunogenic, and non-toxic, and are therefore suitable for such biomedical applications [4]. Cells within this structure survived to the end of the 23-day differentiation process and could secreted albumin, suggesting that the generation of a 3D liver-like structure is a distinct possibility in the near future.

Success! Bioprinting stem cells and their derivatives seem to be feasible, and, therefore, this study could represent an important step towards the generation of replacement human organs. The authors hope to build upon this success, which they highlight as the first to demonstrate that hiPSCs can be bioprinted without adversely affecting their biological functions, and formulate an improved strategy to enhance albumin secretion and 3D organ formation.

References

  1. Faulkner-Jones A, Fyfe C, Cornelissen DJ, et al. Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D. Biofabrication 2015;7:044102.
  2. Faulkner-Jones A, Greenhough S, King JA, et al. Development of a valve-based cell printer for the formation of human embryonic stem cell spheroid aggregates. Biofabrication 2013;5:015013.
  3. Hay DC, Zhao D, Fletcher J, et al. Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells 2008;26:894-902.
  4. Fedorovich NE, Alblas J, de Wijn JR, et al. Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. Tissue Eng 2007;13:1905-1925.