Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury

49Citations
Citations of this article
75Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: It is well understood that hypoxic-ischemic (HI) brain injury during the highly vulnerable perinatal period can lead to cerebral palsy, the most prevalent cause of chronic disability in children. Recently, human clinical trials have reported safety and some efficacy following treatment of cerebral palsy using umbilical cord blood (UCB) cells. UCB is made up of many different cell types, including endothelial progenitor cells (EPCs), T regulatory cells (Tregs), and monocyte-derived suppressor cells (MDSCs). How each cell type contributes individually towards reducing neuroinflammation and/or repairing brain injury is not known. In this study, we examined whether human (h) UCB, or specific UCB cell types, could reduce peripheral and cerebral inflammation, and promote brain repair, when given early after perinatal HI brain injury. Methods: HI brain injury was induced in postnatal day (PND) 7 rat pups and cells were administered intraperitoneally on PND 8. Behavioral testing was performed 7days post injury, and then, brains and spleens were collected for analysis. Results: We found in vitro that all UCB cell types, except for EPCs, were immunomodulatory. Perinatal HI brain injury induced significant infiltration of CD4+ T cells into the injured cerebral hemisphere, and this was significantly reduced by all hUCB cell types tested. Compared to HI, UCB, Tregs, and EPCs were able to reduce motor deficits, reduce CD4+ T cell infiltration into the brain, and reduce microglial activation. In addition to the beneficial effects of UCB, EPCs also significantly reduced cortical cell death, returned CD4+ T cell infiltration to sham levels, and reduced the peripheral Th1-mediated pro-inflammatory shift. Conclusion: This study highlights that cells found in UCB is able to mediate neuroinflammation and is an effective neuroprotective therapy. Our study also shows that particular cells found in UCB, namely EPCs, may have an added advantage over using UCB alone. This work has the potential to progress towards tailored UCB therapies for the treatment of perinatal brain injury.

Cite

CITATION STYLE

APA

McDonald, C. A., Penny, T. R., Paton, M. C. B., Sutherland, A. E., Nekkanti, L., Yawno, T., … Miller, S. L. (2018). Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury. Journal of Neuroinflammation, 15(1). https://doi.org/10.1186/s12974-018-1089-5

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free