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

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

doi:10.1002/adfm.201801850

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

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

Research output: Contribution to journal › Article › peer-review

227 Scopus citations

Abstract

A bioengineered spinal cord is fabricated via extrusion-based multimaterial 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 in vitro and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.

Original language	English (US)
Article number	1801850
Journal	Advanced Functional Materials
Volume	28
Issue number	39
DOIs	https://doi.org/10.1002/adfm.201801850
State	Published - Sep 26 2018

Bibliographical note

Funding Information:
D.J. and V.T. contributed equally to this work. A.M.P. and M.C.M. are cosenior authors. The authors thank David Yang, Elizabeth Smith, Samantha Barkan, and Dr. Susan A. Keirstead for insightful discussions and technical support regarding the 3D bioprinting process, statistical analysis, and the calcium imaging studies. J.R.D., A.M.P., and M.C.M. acknowledge Conquer Paralysis Now, and the Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program. J.R.D. and A.M.P. acknowledge generous support from an anonymous philanthropic donor. M.C.M. acknowledges the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award No. 1DP2EB020537). A.M.P. acknowledges the CTSI KL2 Scholar Program of the National Institutes of Health (Award No. NIHCON000000033119-3002). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

3D bioprinting
induced pluripotent stem cells
neural progenitor cells
spinal cord scaffolds
tissue engineering

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10.1002/adfm.201801850

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title = "3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds",

abstract = "A bioengineered spinal cord is fabricated via extrusion-based multimaterial 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 in vitro and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.",

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note = "Funding Information: D.J. and V.T. contributed equally to this work. A.M.P. and M.C.M. are cosenior authors. The authors thank David Yang, Elizabeth Smith, Samantha Barkan, and Dr. Susan A. Keirstead for insightful discussions and technical support regarding the 3D bioprinting process, statistical analysis, and the calcium imaging studies. J.R.D., A.M.P., and M.C.M. acknowledge Conquer Paralysis Now, and the Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program. J.R.D. and A.M.P. acknowledge generous support from an anonymous philanthropic donor. M.C.M. acknowledges the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award No. 1DP2EB020537). A.M.P. acknowledges the CTSI KL2 Scholar Program of the National Institutes of Health (Award No. NIHCON000000033119-3002). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

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AU - Joung, Daeha

AU - Truong, Vincent

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AU - Guo, Shuang Zhuang

AU - Walsh, Patrick J.

AU - Monat, Joseph R.

AU - Meng, Fanben

AU - Park, Sung Hyun

AU - Dutton, James R.

AU - Parr, Ann M.

AU - McAlpine, Michael C.

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

Abstract

Bibliographical note

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

Abstract

Bibliographical note

Keywords

Publisher link

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Supporting data for "3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds"

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