Combination of human endothelial colony-forming cells and mesenchymal stromal cells exert neuroprotective effects in the growth-restricted newborn

Abstract

The foetal brain is particularly vulnerable to the detrimental effects of foetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure foetal mesenchymal stromal cells (MSC) and endothelial colony-forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of combined MSC-ECFCs (cECFC; 106 ECFC 106 MSC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using MSCs alone. These results demonstrate cECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and may act as a neuroprotectant.

Stem Cell Therapy for Neuroprotection in the Growth-Restricted Newborn

“…However, this treatment did not significantly reduce the increased number of astrocytes present in the brain parenchyma of the FGR piglet. 124 These results are again corroborated by an FGR lamb study where UCB treatment reduced activated microglial cells but had no effect on astrocytes. 123 Furthermore, an FGR rat study also showed that umbilical cord-derived mesenchymal stromal cells (UC-MSC) did not affect the number of astrocytes 7 days after treatment.…”

“…This suggests that eECFC treatment improves brain vasculature without promoting excessive angiogenesis. 124 The same study showed BBB integrity was also improved following cECFC treatment in the FGR piglet with reduced albumin leakage into the brain. 124 Conversely, MSCs delivered alone did not exert a significant effect on improving the vasculature in the brains of FGR piglets 3 days after treatment.…”

“… 124 The same study showed BBB integrity was also improved following cECFC treatment in the FGR piglet with reduced albumin leakage into the brain. 124 Conversely, MSCs delivered alone did not exert a significant effect on improving the vasculature in the brains of FGR piglets 3 days after treatment. In addition to these findings, these human stem cell populations survived in immunocompetent piglets without the need for deleterious immunosuppressive therapy (eg, cyclosporine), emphasizing their potential for non-immunogenic allogeneic transplantation in infants.…”

“…Following cECFC treatment in the FGR piglet, astrocytes displayed a normalized glial vessel interaction similar to the normally grown piglets with consistent contact along the vasculature, suggesting glial cells conversion to a supportive role. 124 While UCB treatment did not alter astrogliosis in the FGR lamb, the authors observed an increased association of smooth muscle proteins of the basal lamina with pericytes in the NVU. 123 …”

“…The authors examined the effects of dual human fetal MSC and endothelial colony-forming cells (ECFC—an EPC) treatment, both isolated from the human placenta, in neonatal FGR piglets. 124 This combination treatment (termed cECFC) resulted in ECFC priming, increasing their homing and engraftment capacity to damage vascular tissue in the brain. Following cECFC treatment, not only was an increase in vessel density evident, but also an improvement in vascular length without vessel branching.…”