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

Myelination by oligodendrocytes (OL) is a key developmental milestone in terms of the functions of the central nervous system (CNS). Demyelination caused by defects in OL 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. OL can be differentiated from pluripotent stem cells; however, there is a lack of efficient culture systems that generate functional OL. 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 brain extracellular matrix (BEM) derived from decellularized human brain tissue enhanced the differentiation of iPSCs into myelin-expressing OL. Co-culture of iPSC-OL with induced neuronal (iN) cells on BEM substrates, which closely mimics the in vivo brain microenviro...