Basic Science Article | Published:

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

Pediatric Research (2019) | Download Citation

Subjects

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.

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Acknowledgements

We would like to thank Jamie Mihelakis, Dalibor Stanojkovic, and Arielle Kogan for their technical assistance. This project was made possible with financial support from the Cerebral Palsy Alliance, Inner Wheel Australia, and the National Health and Medical Research Council, as well as an Australian Research Council Future Fellowship to S.L.M., NHMRC and Cerebral Palsy Alliance Early Career Research Fellowship to C.A.M. and Kahli Sargent Research Studentship and Australian Government Research Training Program Scholarship to M.C.B.P. All included authors met the Pediatric Research authorship requirements.

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Author notes

  1. These authors jointly supervised this work: Suzanne L. Miller, Courtney A. McDonald

Affiliations

  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia

    • Madison C. B. Paton
    • , Beth J. Allison
    • , Michael C. Fahey
    • , Jingang Li
    • , Amy E. Sutherland
    • , Yen Pham
    • , Ilias Nitsos
    • , Robert J. Bischof
    • , Timothy J. Moss
    • , Graeme R. Polglase
    • , Graham Jenkin
    • , Suzanne L. Miller
    •  & Courtney A. McDonald
  2. Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia

    • Madison C. B. Paton
    • , Timothy J. Moss
    • , Graeme R. Polglase
    • , Graham Jenkin
    •  & Suzanne L. Miller
  3. Department of Pediatrics, Monash University, Clayton, VIC, Australia

    • Michael C. Fahey

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The authors declare no competing interests.

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Correspondence to Suzanne L. Miller.

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DOI

https://doi.org/10.1038/s41390-019-0366-z