Induction of regional chemokine expression in response to human umbilical cord blood cell infusion in the neonatal mouse ischemia-reperfusion brain injury model.

Abstract

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury.