To promote the timely regeneration of cells by designing stem cell strategies

A team led by the National Child Health System reports that the brain developed in newborns has certain types of immature progenitor cells that can be expanded and induced to replace brain-injured cells. In a clinical model of early brain injury through recombinant horse proteins, Sirt1 plays a key role in the regeneration of glial cells by endogenous progenitor cells after hypoxia-associated brain injury.

Dr. Vittorio Gallo, director of the National Center for Neuroscience Research in Children, said, "It's not healing. It's about regenerating the lost substance." The first step is to identify cells that can regenerate the loss and then expand its associated endogenous cell proliferation. The percentage of glial progenitor cells in total brain cells was 4 to 5. Considering that the brain consists of billions of cells, this is a considerable number. The advantage is that these progenitor cells already exist, and there is no requirement through the blood-brain barrier, and ultimately they will differentiate into oligodendrocyte white matter and mature glial. That's exactly what we want them to do.

The team found that Sirt1 is a novel modulator of basal oligodendrocyte progenitor cell (OPC) proliferation and an important regulator of neonatal white matter hypoxia. "We also clarified the mechanism by which Sirt1 targets other members of the Cdk2 signaling pathway by modulating their deacetylation, complex formation, and E2F1 release, driving the Cdk2-mediated signaling pathway," said Li-Jin Chew, Ph.D., associate professor of research at the Children's Neuroscience Research Center.

In neonates, hypoxia-induced brain damage initiates spontaneous amplification of progenitor cells but also leads to a lack of mature oligodendrocytes. Inhibition of Sirt1 expression in vitro and in vivo indicates that loss of its deacetylase activity prevents the proliferation of OPC in hypoxia while promoting maturation of oligodendrocytes, emphasizing the importance of delicate balance of Sirt1 activity between maintenance of both processes.

Time is of essence because Sirt1 plays a beneficial role in a certain place (white matter) and at a given time (immature brain continues to develop). "We saw the largest Sirt1 expression and activity in the first week of neonatal brain injury," Gallo said. "There is a very narrow window that uses the stimulus of the amplified progenitor population to target this particular molecule for repair."

The team reports that Sirt1 is a nicotinamide adenine dinucleotide-dependent class III histone deacetylase, known to be involved in normal cell development, aging, inflammatory response, energy metabolism and calorie restriction. Its activity can be regulated by inhibiting the sirtinol protein of the off-the-shelf drug sirtinol. This finding points to the potential of therapeutic interventions for diffuse white matter injury in neonates. "Ideally, we would like to be able to promote the timely regeneration of cells by designing stem cell strategies," Gallo said. By the way, Flarebio offers superior recombinant proteins such as recombinant CDH2.