journal article·2018-11-28Open access

3D Bioprinting Human Induced Pluripotent Stem Cell-Derived Neural Tissues Using a Novel Lab-on-a-Printer Technology

Laura De la Vega, Diego A. Rosas Gómez, Emily Abelseth, Laila Abelseth, Victor Allisson da Silva, Stephanie M. Willerth

Applied Sciences· Volume 8· Issue 12

Abstract

Most neurological diseases and disorders lack true cures, including spinal cord injury (SCI). Accordingly, current treatments only alleviate the symptoms of these neurological diseases and disorders. Engineered neural tissues derived from human induced pluripotent stem cells (hiPSCs) can serve as powerful tools to identify drug targets for treating such diseases and disorders. In this work, we demonstrate how hiPSC-derived neural progenitor cells (NPCs) can be bioprinted into defined structures using Aspect Biosystems’ novel RX1 bioprinter in combination with our unique fibrin-based bioink in rapid fashion as it takes under 5 min to print four tissues. This printing process preserves high levels of cell viability (>81%) and their differentiation capacity in comparison to less sophisticated bioprinting methods. These bioprinted neural tissues expressed the neuronal marker, βT-III (45 ± 20.9%), after 15 days of culture and markers associated with spinal cord (SC) motor neurons (MNs), such as Olig2 (68.8 ± 6.9%), and HB9 (99.6 ± 0.4%) as indicated by flow cytometry. The bioprinted neural tissues expressed the mature MN marker, ChaT, after 30 days of culture as indicated by immunocytochemistry. In conclusion, we have presented a novel method for high throughput production of mature hiPSC-derived neural tissues with defined structures that resemble those found in the SC.
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Research context

OpenAlex topics: 3D Printing in Biomedical Research · Pluripotent Stem Cells Research · Neuroscience and Neural Engineering

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Mechanical Engineering, University of Victoria, BC V8P 5C2, Canada

School of Engineering and Sciences, Monterrey Institute of Technology and Higher Education, Mexico City 14380, Mexico

Biomedical Engineering Program, University of Victoria, BC V8P 5C2, Canada

Center of Mathematics, Computing and Cognition, Federal University of ABC, São Paulo 09606-045, Brazil

Division of Medical Sciences, University of Victoria, BC V8P 5C2, Canada

Funding

Natural Sciences and Engineering Research Council of Canada · Canada Research Chairs · British Columbia Innovation Council

References (35)

Show source-provided references
1. Maitin, I.B., and Cruz, E. (2015). Current Diagnosis & Treatment: Physical Medicine & Rehabilitation, McGraw-Hill Education.
2. (2018, November 02). Spinal Cord Injury. Available online: http://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.
3. Fehlings, M.G., Vaccaro, A.R., Ditunno, J., Vaccaro, A.R., Rossignol, S., and Burns, A. (2012). Essentials of Spinal Cord Injury: Basic Research to Clinical Practice, Thieme Medical Publishers, Incorporated.10.1055/b-0034-83848 ↗
4. Understanding the Presentations and Patterns of Traumatic Spinal Cord Injuries to Develop the Data Collection Format10.1055/s-0038-1649281 ↗
5. Spinal Cord Injury Is Related to an Increased Risk of Multiple Sclerosis: A Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study10.1089/neu.2014.3723 ↗
6. Recent Advances in the Pharmacologic Treatment of Spinal Cord Injury10.1007/s11011-014-9547-y ↗
7. Temenoff, J.S., and Mikos, A.G. (2008). Biomaterials: The Intersection of Biology and Materials Science, Pearson/Prentice Hall.
8. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening10.3389/fbioe.2017.00069 ↗
9. Bioengineered Scaffolds for Spinal Cord Repair10.1089/ten.teb.2010.0648 ↗
10. Three-dimensional bioprinting in tissue engineering and regenerative medicine10.1007/s10529-015-1975-1 ↗
11. Advances in stem cell therapy for spinal cord injury10.1172/JCI64124 ↗
12. Stem Cell-Based Therapies for Spinal Cord Injury10.1080/10790268.2009.11760761 ↗
13. Induced pluripotent stem cells, new tools for drug discovery and new hope for stem cell therapies10.2174/1874467210902010015 ↗
14. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency10.1073/pnas.0910012107 ↗
15. The bioink: A comprehensive review on bioprintable materials10.1016/j.biotechadv.2016.12.006 ↗
16. Mechanically stable fibrin scaffolds promote viability and induce neurite outgrowth in neural aggregates derived from human induced pluripotent stem cells10.1038/s41598-017-06570-9 ↗
17. Chitosan and its derivatives for tissue engineering applications10.1016/j.biotechadv.2007.07.009 ↗
18. 3D Bioprinting Stem Cell Derived Tissues10.1007/s12195-018-0530-2 ↗
19. 3D bioprinting for engineering complex tissues10.1016/j.biotechadv.2015.12.011 ↗
20. Bioprinting for stem cell research10.1016/j.tibtech.2012.10.005 ↗
21. Bsoul, A., Cretu, E., and Walus, K. (2015, January 25–29). Lab-on-a-printer platform technology. Proceedings of the 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Gyeongju, Korea.
22. (2018, September 20). Lab-On-A-Printer. Available online: https://www.aspectbiosystems.com/technology.
23. Takazawa, T., Croft, G.F., Amoroso, M.W., Studer, L., Wichterle, H., and MacDermott, A.B. (2012). Maturation of Spinal Motor Neurons Derived from Human Embryonic Stem Cells. PLoS ONE, 7.10.1371/journal.pone.0040154 ↗
24. DMH1, a Highly Selective Small Molecule BMP Inhibitor Promotes Neurogenesis of hiPSCs: Comparison of PAX6 and SOX1 Expression during Neural Induction10.1021/cn300029t ↗
25. Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells10.1038/ncomms7626 ↗
26. Differentiation of spinal motor neurons from pluripotent human stem cells10.1038/nprot.2009.127 ↗
27. De la Vega, L., Karmirian, K., and Willerth, S.M. (2018). Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres. Adv. Biosyst.10.1002/adbi.201800133 ↗
28. Optimizing Differentiation Protocols for Producing Dopaminergic Neurons from Human Induced Pluripotent Stem Cells for Tissue Engineering Applications: Supplementary Issue: Stem Cell Biology10.4137/BMI.S20064 ↗
29. Guggulsterone-releasing microspheres direct the differentiation of human induced pluripotent stem cells into neural phenotypes10.1088/1748-605X/aaaa77 ↗
30. Channel density and porosity of degradable bridging scaffolds on axon growth after spinal injury10.1016/j.biomaterials.2012.12.002 ↗
31. Electrospun poly (ɛ-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering10.1016/j.biomaterials.2008.08.007 ↗
32. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity10.1073/pnas.1516645112 ↗
33. 3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds10.1002/adfm.201801850 ↗
34. Functional 3D neural mini-tissues from printed gel-based bioink and human neural stem cells10.1002/adhm.201600095 ↗
35. 3D bioprinting human induced pluripotent stem cell constructs for in situ cell proliferation and successive multilineage differentiation10.1002/adhm.201700175 ↗