Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain

  title={Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain},
  author={Martha S. Windrem and Marta Nunes and William K. Rashbaum and Theodore H Schwartz and Robert A Goodman and Guy M. McKhann and Neeta Singh Roy and Steven A. Goldman},
  journal={Nature Medicine},
Both late-gestation and adult human forebrain contain large numbers of oligodendrocyte progenitor cells (OPCs). These cells may be identified by their A2B5+PSA-NCAM− phenotype (positive for the early oligodendrocyte marker A2B5 and negative for the polysialylated neural cell adhesion molecule). We used dual-color fluorescence-activated cell sorting (FACS) to extract OPCs from 21- to 23-week-old fetal human forebrain, and A2B5 selection to extract these cells from adult white matter. When… 
Human fetal oligodendrocyte progenitor cells from different gestational stages exhibit substantially different potential to myelinate.
Findings indicate that intrinsic regulatory mechanisms associated with the chronological age of the donor cells are key variables to assess when considering the myelination capacity of OPCs for cellular replacement therapy.
Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination.
Human neural progenitors from different foetal forebrain regions remyelinate the adult mouse spinal cord.
In situ, in vitro and in vivo approaches combined to assess the oligodendrogenic potential of different human foetal forebrain regions during the first trimester of gestation reveal the great capacity of human neural progenitors to survive, extensively migrate and successfully remyelinate the spinal cord irrespective of their origin.
CD140a identifies a population of highly myelinogenic, migration-competent, and efficiently engrafting human oligodendrocyte progenitor cells
Transplanted CD140a+ cells were highly migratory and robustly myelinated the hypomyelinated shiverer mouse brain more rapidly and efficiently than did A2B5+cells, suggesting that CD9+/CD140a- cells may constitute an even more highly enriched population of myelinogenic progenitor cells.
Derivation of oligodendrocyte precursor cells from human bone marrow stromal cells and use for re-myelination in the congenitally dysmyelinated brain
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.
Fate determination of adult human glial progenitor cells.
Using the transcriptional profiles of acutely isolated GPCs, this work has begun to understand the operative ligand-receptor interactions involved in these processes, and has identified several key signaling pathways by which adult human GPC’s may be reliably instructed to either oligodendrocytic or astrogliotic fate.
β4 Tubulin Identifies a Primitive Cell Source for Oligodendrocytes in the Mammalian Brain
It is proposed that βT4 cells are an endogenous cell source that can be recruited to promote neural repair in the adult telencephalon and provide in vivo support for the therapeutic potential of βT 4 cells.


Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity.
  • S. Zhang, B. Ge, I. Duncan
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
Phenotypic characterization indicated that these OPs resembled neonatal rather than adult OPs and produced robust myelin after transplantation, opening an avenue to explore the potential of these cells for repairing myelin disorders in adulthood.
Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain
L Lentiviral tagging with green fluorescent protein confirmed that A2B5‐sorted progenitors develop myelin basic protein expression within regions of demyelination and that they fail to migrate when implanted into normal brain.
Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain
It is found that adult human white-matter progenitor cells (WMPCs) could be passaged as neurospheres in vitro and that these cells generated functionally competent neurons and glia both in vivo and after xenograft to the fetal rat brain.
Identification, Isolation, and Promoter-Defined Separation of Mitotic Oligodendrocyte Progenitor Cells from the Adult Human Subcortical White Matter
The human subcortical white matter harbors mitotically competent progenitor cells, which give rise primarily to oligodendrocytes in vitro, which may be extracted and purified from adult human white matter in sufficient numbers for implantation and cell-based therapy.
Myelination by transplanted human and mouse central nervous system tissue after long-term cryopreservation
Cryopreservation over 5 years did not impede the graft's ability to produce myelin and can be considered for long-term storage of oligodendrocytes in view of cell therapy.
Oligodendrocyte precursors survive poorly and do not migrate following transplantation into the normal adult central nervous system
The observed behaviour of oligodendrocyte precursors in normal adult tissue is in contrast to their behaviour in myelin mutants and neonates, but mimics the behaviour of the O‐2A progenitor‐like cell line, CG4, following transplantation into similar environments.
Transplantation of Human Embryonic Oligodendrocytes into Shiverer Brain a
By using intracerebral transplantation techniques, it is possible to create a situation in which human oligodendrocytes at a premyelinating stage in situ are placed in a myelinforming mouse brain.
Intraventricular transplantation of oligodendrocyte progenitors into a fetal myelin mutant results in widespread formation of myelin
Data suggest that myelin repair might be achieved by intraventricular delivery and transependymal incorporation of myelin‐producing cells, and similar ex vivo manipulation with genes known to promote survival, migration, or proliferation of the transplanted cells could be used to enhance repair.
Identification and characterization of neuronal precursors and their progeny from human fetal tissue
Overall, HNPs resemble NRPs isolated from rodent tissue and appear to be a neuronal precursor population.
Transplanting oligodendrocyte progenitors into the adult CNS
Although the normal adult CNS does not appear to support survival and migration of the CG4 cell line, it is possible to manipulate the environment in such a way that these nonpermissive properties of the environment can be overcome.