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Derivation of oligodendrocyte precursor cells from human bone marrow stromal cells and use for re-myelination in the congenitally dysmyelinated brain
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Derivation of oligodendrocyte precursor cells from human bone marrow stromal cells and use for re-myelination in the congenitally dysmyelinated brain
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Derivation of oligodendrocyte precursor cells from human bone marrow stromal cells and use for re-myelination in the congenitally dysmyelinated brain
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Paper
Derivation of oligodendrocyte precursor cells from human bone marrow stromal cells and use for re-myelination in the congenitally dysmyelinated brain
2019
Overview
Oligodendrocytes (OLs) are the only myelinating glia in the central nervous system (CNS). In congenital myelin disorders, OL dysfunction or death results in loss of myelin. This causes progressive and irreversible impairment to motor and cognitive functions, and is amongst the most disabling neurological disorder. Neonatal engraftment by glial progenitor cells (GPCs) allows the robust myelination of congenitally dysmyelinated brain, thereby preserving brain function and quality of life of patients. However, endogenous sources of glial progenitors are hard to obtain without causing secondary injury, while use of exogenous sources such as embryonic stem cells and induced-pluripotent stem cells face considerable ethical and safety issues. To circumvent such hurdles, we asked whether NG2+ cells in the bone marrow could be a potential cell source for GPCs. We successfully generated glial progenitor cells (GPCs) from human bone marrow stromal cells (hBMSCs) from 3 donors using a 14-day induction protocol. The generated hBMSC-GPCs were highly enriched in OPC marker expression, including OLIG2, PDGFRα, NG2, SOX10 and O4, and showed efficient differentiation into myelinogenic oligodendrocytes when transplanted into postnatal day 7 (P7) myelin-deficient shiverer mice. Remyelination of the shiverer mouse brain significantly extended lifespan and improved motor function. The novel induction protocol described here provides a method for fast, simple and effective glial therapy for myelin disorders, overcoming existent hurdles of cell source restriction and time frame requirement.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
/ Neonates
