Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Comparative analysis of umbilical cord blood cells vs mesenchymal stromal cells for inflammation-induced preterm brain injury (#29)

Madison Paton 1 2 , Jingang Li 1 , Beth Allison 1 , Michael Fahey 3 , Amy Sutherland 1 , Tamara Yawno 1 , Robert Bischoff 1 , Ilias Nitsos 1 , Timothy Moss 1 , Graeme Polglase 1 , Graham Jenkin 1 2 , Suzanne Miller 1 2 , Courtney McDonald 1
  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Department of Obstetrics and Gynaecology, Monash University , Clayton, VIC, Australia
  3. Department of Paediatrics, Monash University, Clayton, VIC, Australia

Background

There are currently over 100 clinical trials investigating stem cells for the treatment of neurological conditions, but despite many years of study, they have not yet progressed into routine clinical use. One potential reason is a lack of knowledge of the optimal cell source. In this study, we aimed to directly compare the potential of umbilical cord blood (UCB) cells and mesenchymal stromal cells (MSCs) to reduce inflammation and brain injury in a large animal model of inflammation-induced preterm brain injury.

 

Methods

Chronically instrumented fetal sheep at 0.65 gestation were administered intravenous lipopolysaccharide (LPS:150ng) or saline, over 3 consecutive days.6hoursafterthefinalLPSdose, fetuses received IV either 100 million human UCB cells or 10 million human cord tissue-derivedMSCs. Physiological recordings and plasma were collected throughout the experiment. 7 days after cell treatment, CSFwascollected,andbrainsprocessedforhistologicalanalysisofwhitematter.

 

Results

Neuroinflammation and cell death was evident in the white matter following LPS administration. UCB and MSC treatment were similarly able to significantly reduce microglial aggregations, neutrophil recruitment, cytokine concentrations and cell death.

Within white matter, LPS administration significantly reduced total oligodendrocyte cell counts (Olig-2). LPS led to a reduction in the number of mature oligodendrocytes (MBP, O1) and increased immature oligodendrocytes (O4). Treatment with UCB cells was able to ameliorate these deficits; restoring total oligodendrocyte cell counts and normalizing oligodendrocyte maturation. Interestingly, MSCs were not able to restore white matter deficits.

 

Conclusion

Our results support previous findings that MSCs and UCB cells can reduce neuroinflammation. However, MSCs were not as effective as UCB cells for repairing white matter injury and restoring normal oligodendrocyte maturation. This work highlights that consideration is required before selecting which cell source is used for clinical applications such as the preterm white matter injury.