Pediatr Res. 2019 Mar 11. doi: 10.1038/s41390-019-0366-z. [Epub ahead of print]

Umbilical cord blood versus mesenchymal stem cells for inflammation-induced preterm brain injury in fetal sheep.

Paton MCB^1,2, Allison BJ¹, Fahey MC^1,3, Li J¹, Sutherland AE¹, Pham Y¹, Nitsos I¹, Bischof RJ¹, Moss TJ^1,2, Polglase GR^1,2, Jenkin G^1,2, Miller SL^4,5, McDonald CA¹.

Abstract

BACKGROUND:

Chorioamnionitis and fetal inflammation are principal causes of neuropathology detected after birth, particularly in very preterm infants. Preclinical studies show that umbilical cord blood (UCB) cells are neuroprotective, but it is uncertain if allogeneic UCB cells are a feasible early intervention for preterm infants. In contrast, mesenchymal stem cells (MSCs) are more readily accessible and show strong anti-inflammatory benefits. We aimed to compare the neuroprotective benefits of UCB versus MSCs in a large animal model of inflammation-induced preterm brain injury. We hypothesized that MSCs would afford greater neuroprotection.

METHODS:

Chronically instrumented fetal sheep at 0.65 gestation received intravenous lipopolysaccharide (150 ng; 055:B5, n = 8) over 3 consecutive days; or saline for controls (n = 8). Cell-treated animals received 10⁸ UCB mononuclear cells (n = 7) or 10⁷ umbilical cord MSCs (n = 8), intravenously, 6 h after the final lipopolysaccharide dose. Seven days later, cerebrospinal fluid and brain tissue was collected for analysis.

RESULTS:

Lipopolysaccharide induced neuroinflammation and apoptosis, and reduced the number of mature oligodendrocytes. MSCs reduced astrogliosis, but UCB did not have the same effect. UCB significantly decreased cerebral apoptosis and protected mature myelinating oligodendrocytes, but MSCs did not.

CONCLUSION:

UCB appears to better protect white matter development in the preterm brain in response to inflammation-induced brain injury in fetal sheep.