3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

Overview

Journal Adv Funct Mater

Date 2020 Jun 30

PMID 32595422

Citations 96

Authors

Daeha Joung

Vincent Truong

Colin C Neitzke

Shuang-Zhuang Guo

Patrick J Walsh

Joseph R Monat

Fanben Meng

Sung Hyun Park

James R Dutton

Ann M Parr

Michael C McAlpine

Affiliations

Soon will be listed here.

Abstract

A bioengineered spinal cord is fabricated via extrusion-based multi-material 3D bioprinting, in which clusters of induced pluripotent stem cell (iPSC)-derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) are placed in precise positions within 3D printed biocompatible scaffolds during assembly. The location of a cluster of cells, of a single type or multiple types, is controlled using a point-dispensing printing method with a 200 μm center-to-center spacing within 150 μm wide channels. The bioprinted sNPCs differentiate and extend axons throughout microscale scaffold channels, and the activity of these neuronal networks is confirmed by physiological spontaneous calcium flux studies. Successful bioprinting of OPCs in combination with sNPCs demonstrates a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system (CNS) tissue damage. This platform can be used to prepare novel biomimetic, hydrogel-based scaffolds modeling complex CNS tissue architecture and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.

Citing Articles

Microalgae-enriched (bio)inks for 3D bioprinting of cultured seafood.

Marques D, Jabouille M, Gusmao A, Leite M, Sanjuan-Alberte P, Ferreira F NPJ Sci Food. 2025; 9(1):23.

PMID: 39939615 PMC: 11821890. DOI: 10.1038/s41538-025-00386-y.

3D bioprinted dynamic bioactive living construct enhances mechanotransduction-assisted rapid neural network self-organization for spinal cord injury repair.

Yang J, Kim K, Liu Y, Luo X, Ma C, Man W Bioact Mater. 2025; 46:531-554.

PMID: 39886605 PMC: 11780150. DOI: 10.1016/j.bioactmat.2024.12.028.

Bioprinting of a multi-composition array to mimic intra-tumor heterogeneity of glioblastoma for drug evaluation.

Lee G, Kim S, Choi Y, Park J, Park J Microsyst Nanoeng. 2024; 10(1):186.

PMID: 39663377 PMC: 11634888. DOI: 10.1038/s41378-024-00843-w.

Hyaluronic Acid-Based 3D Bioprinted Hydrogel Structure for Directed Axonal Guidance and Modeling Innervation In Vitro.

Honkamaki L, Kulta O, Puistola P, Hopia K, Emeh P, Isosaari L Adv Healthc Mater. 2024; 14(1):e2402504.

PMID: 39502022 PMC: 11694092. DOI: 10.1002/adhm.202402504.

Innovative Strategies in 3D Bioprinting for Spinal Cord Injury Repair.

Kim D, Liu Y, Kim G, An S, Han I Int J Mol Sci. 2024; 25(17).

PMID: 39273538 PMC: 11395085. DOI: 10.3390/ijms25179592.

References

Thomas M, Willerth S . 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening. Front Bioeng Biotechnol. 2017; 5:69. PMC: 5698280. DOI: 10.3389/fbioe.2017.00069. View

Ahuja C, Fehlings M . Concise Review: Bridging the Gap: Novel Neuroregenerative and Neuroprotective Strategies in Spinal Cord Injury. Stem Cells Transl Med. 2016; 5(7):914-24. PMC: 4922857. DOI: 10.5966/sctm.2015-0381. View

Dulin J, Adler A, Kumamaru H, Poplawski G, Lee-Kubli C, Strobl H . Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts. Nat Commun. 2018; 9(1):84. PMC: 5758751. DOI: 10.1038/s41467-017-02613-x. View

Langer R, Vacanti J . Tissue engineering. Science. 1993; 260(5110):920-6. DOI: 10.1126/science.8493529. View

Parr A, Kulbatski I, Zahir T, Wang X, Yue C, Keating A . Transplanted adult spinal cord-derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury. Neuroscience. 2008; 155(3):760-70. DOI: 10.1016/j.neuroscience.2008.05.042. View

Winter C, Katiyar K, Hernandez N, Song Y, Struzyna L, Harris J . Transplantable living scaffolds comprised of micro-tissue engineered aligned astrocyte networks to facilitate central nervous system regeneration. Acta Biomater. 2016; 38:44-58. PMC: 5457669. DOI: 10.1016/j.actbio.2016.04.021. View

Walsh P, Truong V, Hill C, Stoflet N, Baden J, Low W . Defined Culture Conditions Accelerate Small-molecule-assisted Neural Induction for the Production of Neural Progenitors from Human-induced Pluripotent Stem Cells. Cell Transplant. 2018; 26(12):1890-1902. PMC: 5802631. DOI: 10.1177/0963689717737074. View

Gelain F, Panseri S, Antonini S, Cunha C, Donega M, Lowery J . Transplantation of nanostructured composite scaffolds results in the regeneration of chronically injured spinal cords. ACS Nano. 2010; 5(1):227-36. DOI: 10.1021/nn102461w. View

Zhu W, George J, Sorger V, Zhang L . 3D printing scaffold coupled with low level light therapy for neural tissue regeneration. Biofabrication. 2017; 9(2):025002. DOI: 10.1088/1758-5090/aa6999. View

10.

Knowlton S, Anand S, Shah T, Tasoglu S . Bioprinting for Neural Tissue Engineering. Trends Neurosci. 2017; 41(1):31-46. DOI: 10.1016/j.tins.2017.11.001. View

11.

Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D . Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012; 150(6):1264-73. PMC: 3445432. DOI: 10.1016/j.cell.2012.08.020. View

12.

Gros T, Sakamoto J, Blesch A, Havton L, Tuszynski M . Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds. Biomaterials. 2010; 31(26):6719-29. DOI: 10.1016/j.biomaterials.2010.04.035. View

13.

Kadoya K, Lu P, Nguyen K, Lee-Kubli C, Kumamaru H, Yao L . Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med. 2016; 22(5):479-87. PMC: 4860037. DOI: 10.1038/nm.4066. View

14.

Kolesky D, Homan K, Skylar-Scott M, Lewis J . Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci U S A. 2016; 113(12):3179-84. PMC: 4812707. DOI: 10.1073/pnas.1521342113. View

15.

Johnson B, Lancaster K, Hogue I, Meng F, Kong Y, Enquist L . 3D printed nervous system on a chip. Lab Chip. 2015; 16(8):1393-400. PMC: 4829438. DOI: 10.1039/c5lc01270h. View

16.

de Ruiter G, Onyeneho I, Liang E, Moore M, Knight A, Malessy M . Methods for in vitro characterization of multichannel nerve tubes. J Biomed Mater Res A. 2007; 84(3):643-51. DOI: 10.1002/jbm.a.31298. View

17.

Agmon G, Christman K . Controlling stem cell behavior with decellularized extracellular matrix scaffolds. Curr Opin Solid State Mater Sci. 2016; 20(4):193-201. PMC: 4979580. DOI: 10.1016/j.cossms.2016.02.001. View

18.

Giger R, Hollis 2nd E, Tuszynski M . Guidance molecules in axon regeneration. Cold Spring Harb Perspect Biol. 2010; 2(7):a001867. PMC: 2890195. DOI: 10.1101/cshperspect.a001867. View

19.

Teng Y, Lavik E, Qu X, Park K, Ourednik J, Zurakowski D . Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A. 2002; 99(5):3024-9. PMC: 122466. DOI: 10.1073/pnas.052678899. View

20.

Hopkins A, DeSimone E, Chwalek K, Kaplan D . 3D in vitro modeling of the central nervous system. Prog Neurobiol. 2014; 125:1-25. PMC: 4324093. DOI: 10.1016/j.pneurobio.2014.11.003. View