Aligned Brain Extracellular Matrix Promotes Differentiation and Myelination of Human-Induced Pluripotent Stem Cell-Derived Oligodendrocytes

Ann Na Cho, Yoonhee Jin, Suran Kim, Sajeesh Kumar, Heungsoo Shin, Hoon Chul Kang, Seung Woo Cho

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Myelination by oligodendrocytes (OLs) is a key developmental milestone in terms of the functions of the central nervous system (CNS). Demyelination caused by defects in OLs is a hallmark of several CNS disorders. Although a potential therapeutic strategy involves treatment with the myelin-forming cells, there is no readily available source of these cells. OLs can be differentiated from pluripotent stem cells; however, there is a lack of efficient culture systems that generate functional OLs. Here, we demonstrate biomimetic approaches to promote OL differentiation from human-induced pluripotent stem cells (iPSCs) and to enhance the maturation and myelination capabilities of iPSC-derived OL (iPSC-OL). Functionalization of culture substrates using the brain extracellular matrix (BEM) derived from decellularized human brain tissue enhanced the differentiation of iPSCs into myelin-expressing OLs. Co-culture of iPSC-OL with induced neuronal (iN) cells on BEM substrates, which closely mimics the in vivo brain microenvironment for myelinated neurons, not only enhanced myelination of iPSC-OL but also improved electrophysiological function of iN cells. BEM-functionalized aligned electrospun nanofibrous scaffolds further promoted the maturation of iPSC-OLs, enhanced the production of myelin sheath-like structures by the iPSC-OL, and enhanced the neurogenesis of iN cells. Thus, the biomimetic strategy presented here can generate functional OLs from stem cells and facilitate myelination by providing brain-specific biochemical, biophysical, and structural signals. Our system comprising stem cells and brain tissue from human sources could help in the establishment of human demyelination disease models and the development of regenerative cell therapy for myelin disorders.

Original languageEnglish
Pages (from-to)15344-15353
Number of pages10
JournalACS Applied Materials and Interfaces
Volume11
Issue number17
DOIs
StatePublished - 2019 May 1

Fingerprint

Stem cells
Brain
Biomimetics
Neurology
Cell culture
Tissue
Substrates
Scaffolds (biology)
Neurons
Defects

Keywords

  • aligned nanofiber
  • human brain extracellular matrix
  • human-induced pluripotent stem cells
  • induced neuronal cells
  • myelination
  • oligodendrocytes

Cite this

Cho, Ann Na ; Jin, Yoonhee ; Kim, Suran ; Kumar, Sajeesh ; Shin, Heungsoo ; Kang, Hoon Chul ; Cho, Seung Woo. / Aligned Brain Extracellular Matrix Promotes Differentiation and Myelination of Human-Induced Pluripotent Stem Cell-Derived Oligodendrocytes. In: ACS Applied Materials and Interfaces. 2019 ; Vol. 11, No. 17. pp. 15344-15353.
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abstract = "Myelination by oligodendrocytes (OLs) is a key developmental milestone in terms of the functions of the central nervous system (CNS). Demyelination caused by defects in OLs is a hallmark of several CNS disorders. Although a potential therapeutic strategy involves treatment with the myelin-forming cells, there is no readily available source of these cells. OLs can be differentiated from pluripotent stem cells; however, there is a lack of efficient culture systems that generate functional OLs. Here, we demonstrate biomimetic approaches to promote OL differentiation from human-induced pluripotent stem cells (iPSCs) and to enhance the maturation and myelination capabilities of iPSC-derived OL (iPSC-OL). Functionalization of culture substrates using the brain extracellular matrix (BEM) derived from decellularized human brain tissue enhanced the differentiation of iPSCs into myelin-expressing OLs. Co-culture of iPSC-OL with induced neuronal (iN) cells on BEM substrates, which closely mimics the in vivo brain microenvironment for myelinated neurons, not only enhanced myelination of iPSC-OL but also improved electrophysiological function of iN cells. BEM-functionalized aligned electrospun nanofibrous scaffolds further promoted the maturation of iPSC-OLs, enhanced the production of myelin sheath-like structures by the iPSC-OL, and enhanced the neurogenesis of iN cells. Thus, the biomimetic strategy presented here can generate functional OLs from stem cells and facilitate myelination by providing brain-specific biochemical, biophysical, and structural signals. Our system comprising stem cells and brain tissue from human sources could help in the establishment of human demyelination disease models and the development of regenerative cell therapy for myelin disorders.",
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Aligned Brain Extracellular Matrix Promotes Differentiation and Myelination of Human-Induced Pluripotent Stem Cell-Derived Oligodendrocytes. / Cho, Ann Na; Jin, Yoonhee; Kim, Suran; Kumar, Sajeesh; Shin, Heungsoo; Kang, Hoon Chul; Cho, Seung Woo.

In: ACS Applied Materials and Interfaces, Vol. 11, No. 17, 01.05.2019, p. 15344-15353.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Cho, Ann Na

AU - Jin, Yoonhee

AU - Kim, Suran

AU - Kumar, Sajeesh

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AU - Kang, Hoon Chul

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