Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development

Abstract

Background Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth. Objective To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells. Methods Using cell sorting technology, we obtained NG2+/−, A2B5+/− cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice. Results The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/−, A2B5+/− cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5− > NG2− > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2− > A2B5− > A2B5+ > NG2+. Conclusion In summary, NG2+ and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.

Intrauterine desensitization enables long term survival of human oligodendrocyte progenitor cells without immunosuppression

“…However, this approach that contains the initial xenografts before complete immune development of the host and the second xenografts derived from the same species of the initial one did not always result in long-term xenograft survival which depends on the species of donor, the origin of the cells, 3 , 6 , 7 and the strain of the host. 21 There are reports of failure to induce immune tolerance after desensitization.…”

“… 5 Transplantation of exogenous hOPCs can effectively promote myelin repair. 6 For example, transplanting hOPCs into neonatal Shiverer mice can promote cerebral myelination in congenital demyelination 7 ; embryonic stem cell (ESC)-derived OLs transplanted into Sprague-Dawley (SD) rats can migrate into white matter and repair white matter structure and function 8 ; transplantation of hOPCs restored neurobehavioral functions by preventing axonal demyelination in SD rats. 9 hOPCs can be used in the cell therapy of perinatal hypoxic-ischemic and infectious brain injuries, including periventricular leukomalacia and cerebral palsy.…”

Transplanted Human Oligodendrocyte Progenitor Cells Restore Neurobehavioral Deficits in a Rat Model of Preterm White Matter Injury

“…Briefly, hNSCs were isolated from the cortex of human embryos aged 10–13 weeks and amplified in the NSC medium. To generate hOPCs, hNSCs were cultured for 10 days to form neurospheres, which were dissociated into single cells and induced to differentiate in the differentiation medium ( 19 ). The purity of the hOPCs was 80–90%, as confirmed in our previous study ( 20 ).…”

A2B5 Expression in Central Nervous System and Gliomas

“…There are, however, some studies focusing on cells expressing these markers but they mainly concern in vitro experiments. As an example, Zhou et al [71] have characterized A2B5+, A2B5-, NG2+ and NG2-cells obtained from NSCs derived from the human fetal brain after in vitro differentiation into OPCs. In the whole cell population, flow cytometry demonstrated that PDGFRα expression was recorded on up to 75% of the cells, whereas A2B5+ cells accounted for approximately 26% and NG2 for 15%.…”