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Name

Means and methods for the generation of oligodendrocytes

Organization name

Clinic Invent

Profile

Introduction

Oligodendroglial lineage cells (OL) play a key role in myelin related diseases including multiple sclerosis (MS), leukodystrophies as well as periventricular leukomalacia, and there is an increasing awareness of their potential role in neurodegenerative diseases. There is a great need for an improved availability of human OL, especially patient-specific OL. In general, provision of oligodendroglial lineage cells would permit studies to delineate mechanisms regulating repair by endogenous myelin lineage cells and/or provide a source of autologous cells for replacement therapy. Such cells would also provide new opportunities to identify pathological mechanisms underlying de- or dysmyelinating diseases.

Invention

We found a rapid and efficient protocol that facilitatesthe generation of human oligodendrogliallineage cells from human iPSC-derived neural progenitor cells (NPC) using the transcription factor (TF) SOX10. Using a combination of three TFs, this can even be achieved within 28 days with an efficiency of up to 70%. Furthermore, 30% of the O4+ OL differentiate into mature myelin basic protein positive (MBP+) OL within seven additional days. The induced human oligodendroglial lineage cells (iOL) are suitable for in vitro myelination assays using nanofibers or iPSC-derived neurons. After transplantation into MBP deficient shiverer mice iOL disperse widely and myelinate the developmental central nervous system (CNS) as well as the adult demyelinated spinal cord. Furthermore, iOL can be used for disease modeling and to test the potential of pharmacological compounds in promoting oligodendroglial differentiation.

Patent situation

A PCT application has been filed.

Advantages of the invention

  • accelerated generation of OL from iPSC-derived NPC
  • generated cells are suitable for disease modeling and pharmacological screens
  • facilitates the development of high-throughput screening platforms, the study of human myelin diseases and repair strategies using patient-derived iPSC

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