A Culture System to Study Oligodendrocyte Myelination Processes Using Engineered Nanofibers

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2012 Jul 17

PMID 22796663

Citations 196

Authors

Seonok Lee

Michelle K Leach

Stephanie A Redmond

S Y Christin Chong

Synthia H Mellon

Samuel J Tuck

Zhang-Qi Feng

Joseph M Corey

Jonah R Chan

Affiliations

Soon will be listed here.

Abstract

Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive to myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment before differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination.

Citing Articles

Bdnf-Ntrk2 Signaling Promotes but is not Essential for Spinal Cord Myelination in Larval Zebrafish.

Russell K, Kearns C, Walker M, Knoeckel C, Ribera A, Doll C bioRxiv. 2025; .

PMID: 40027741 PMC: 11870533. DOI: 10.1101/2025.02.19.639062.

Protocol for assessing myelination by human iPSC-derived oligodendrocytes in Shiverer mouse ex vivo brain slice cultures.

Tsarouchas T, Zoupi L, Williams A, Gibson E STAR Protoc. 2025; 6(1):103609.

PMID: 39888721 PMC: 11834085. DOI: 10.1016/j.xpro.2025.103609.

Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons.

Yang M, Martin C, Kowsari K, Jagielska A, Van Vliet K PLoS One. 2025; 20(1):e0290521.

PMID: 39854563 PMC: 11759361. DOI: 10.1371/journal.pone.0290521.

Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes.

Bin J, Emberley K, Buscham T, Eichel-Vogel M, Doan R, Steyer A bioRxiv. 2025; .

PMID: 39829751 PMC: 11741303. DOI: 10.1101/2025.01.10.632348.

Guiding Oligodendrocyte Progenitor Cell Maturation Using Electrospun Fiber Cues in a 3D Hyaluronic Acid Hydrogel Culture System.

Mazur R, Lampe K ACS Biomater Sci Eng. 2024; 11(2):1025-1037.

PMID: 39705601 PMC: 11815632. DOI: 10.1021/acsbiomaterials.4c01455.

References

Ruit K, ELLIOTT J, Osborne P, Yan Q, Snider W . Selective dependence of mammalian dorsal root ganglion neurons on nerve growth factor during embryonic development. Neuron. 1992; 8(3):573-87. DOI: 10.1016/0896-6273(92)90284-k. View

Jiang F, Frederick T, Wood T . IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle. Dev Biol. 2001; 232(2):414-23. DOI: 10.1006/dbio.2001.0208. View

Howe C . Coated glass and vicryl microfibers as artificial axons. Cells Tissues Organs. 2006; 183(4):180-94. DOI: 10.1159/000096509. View

Colognato H, Ramachandrappa S, Olsen I, ffrench-Constant C . Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. J Cell Biol. 2004; 167(2):365-75. PMC: 2172535. DOI: 10.1083/jcb.200404076. View

Colello R, Pott U . Signals that initiate myelination in the developing mammalian nervous system. Mol Neurobiol. 1997; 15(1):83-100. DOI: 10.1007/BF02740617. View

Voyvodic J . Target size regulates calibre and myelination of sympathetic axons. Nature. 1989; 342(6248):430-3. DOI: 10.1038/342430a0. View

Lewallen K, Shen Y, De la Torre A, Ng B, Meijer D, Chan J . Assessing the role of the cadherin/catenin complex at the Schwann cell-axon interface and in the initiation of myelination. J Neurosci. 2011; 31(8):3032-43. PMC: 3758556. DOI: 10.1523/JNEUROSCI.4345-10.2011. View

Remahl S, Hildebrand C . Changing relation between onset of myelination and axon diameter range in developing feline white matter. J Neurol Sci. 1982; 54(1):33-45. DOI: 10.1016/0022-510x(82)90216-7. View

Nave K, Trapp B . Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008; 31:535-61. DOI: 10.1146/annurev.neuro.30.051606.094309. View

10.

Bullock P, Rome L . Glass micro-fibers: a model system for study of early events in myelination. J Neurosci Res. 1990; 27(3):383-93. DOI: 10.1002/jnr.490270317. View

11.

Spiegel I, Peles E . A novel method for isolating Schwann cells using the extracellular domain of Necl1. J Neurosci Res. 2009; 87(15):3288-96. PMC: 2760645. DOI: 10.1002/jnr.21985. View

12.

Nave K . Myelination and support of axonal integrity by glia. Nature. 2010; 468(7321):244-52. DOI: 10.1038/nature09614. View

13.

FRIEDE R . Control of myelin formation by axon caliber (with a model of the control mechanism). J Comp Neurol. 1972; 144(2):233-52. DOI: 10.1002/cne.901440207. View

14.

de Waegh S, Lee V, Brady S . Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells. Cell. 1992; 68(3):451-63. DOI: 10.1016/0092-8674(92)90183-d. View

15.

Fruttiger M, Calver A, Richardson W . Platelet-derived growth factor is constitutively secreted from neuronal cell bodies but not from axons. Curr Biol. 2000; 10(20):1283-6. DOI: 10.1016/s0960-9822(00)00757-0. View

16.

Garcia M, Lobsiger C, Shah S, Deerinck T, Crum J, Young D . NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth. J Cell Biol. 2003; 163(5):1011-20. PMC: 2173620. DOI: 10.1083/jcb.200308159. View

17.

Garcia M, Rao M, Fujimoto J, Garcia V, Shah S, Crum J . Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth. J Neurosci. 2009; 29(5):1277-84. PMC: 2782950. DOI: 10.1523/JNEUROSCI.3765-08.2009. View

18.

Corey J, Gertz C, Wang B, Birrell L, Johnson S, Martin D . The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons. Acta Biomater. 2008; 4(4):863-75. PMC: 2922842. DOI: 10.1016/j.actbio.2008.02.020. View

19.

Chan J, Watkins T, Cosgaya J, Zhang C, Chen L, Reichardt L . NGF controls axonal receptivity to myelination by Schwann cells or oligodendrocytes. Neuron. 2004; 43(2):183-91. PMC: 2758239. DOI: 10.1016/j.neuron.2004.06.024. View

20.

Rosenberg S, Kelland E, Tokar E, De la Torre A, Chan J . The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation. Proc Natl Acad Sci U S A. 2008; 105(38):14662-7. PMC: 2567234. DOI: 10.1073/pnas.0805640105. View