Abstract
Advances in prenatal molecular testing have made it possible to diagnose most genetic disorders early in gestation. In utero mesenchymal stem cell (MSC) therapy can be a powerful tool to cure the incurable. With this in mind, this method could ameliorate potential physical and functional damage. However, the presence of maternal T cells trafficking in the fetus during pregnancy is thought to be the major barrier to achieving the engraftment into the fetus. We investigated the possibility of using maternal adipose-derived stem cells (ADSCs) for in utero transplantation to improve engraftment, thus lowering the risk of graft rejection. Herein, fetal brain engraftment using congenic and maternal ADSC grafts was examined via in utero stem cell transplantation in a mouse model. ADSCs were purified using the mesenchymal stem cell markers, PDGFRα, and Sca-1 via fluorescence-activated cell sorting. The PDGFRα+Sca-1+ ADSCs were transplanted into the fetal intracerebroventricular (ICV) at E14.5. The transplanted grafts grew for at least 28 days after in utero transplantation with PDGFRα+Sca-1+ ADSC, and mature neuronal markers were also detected in the grafts. Furthermore, using the maternal sorted ADSCs suppressed the innate immune response, preventing the infiltration of CD8 T cells into the graft. Thus, in utero transplantation into the fetal ICV with the maternal PDGFRα+Sca-1+ ADSCs may be beneficial for the treatment of congenital neurological diseases because of the ability to reduce the responses after in utero stem cell transplantation and differentiate into neuronal lineages.
Highlights
Neurometabolic disorders in children differ from those in adults in that most are autosomal recessively inherited, and few have X-linked inheritance [1]
These results suggest that PDGFRαþSca-1þ adipose-derived stem cells (ADSCs) might have the potential to differentiate into neural lineage cells in the aggregation culture
IL-10 modulates the production by T cells of pro-inflammatory molecules, like TNFα and IL-1 β [34]. These results suggest that maternal PDGFRαþSca-1þ ADSC grafts can be used as the donor cells for in utero transplantation to suppress the recipient's immune system, including maternal immunity more than PDGFRαþSca-1þ ADSC grafts from green congenic mice
Summary
Neurometabolic disorders in children differ from those in adults in that most are autosomal recessively inherited, and few have X-linked inheritance [1]. These disorders may be catabolic and anabolic conditions, some of which combine maldevelopment and degenerative features [2]. When considering how to treat neurometabolic disorders in infants with effective results, in utero transplantation using MSCs is deployed to treat symptoms. This can prevent disease onset and avoid the devastating manifestations that would otherwise occur before birth
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