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.
Highlights
Cerebral palsy (CP) is a permanent movement disorder caused by abnormal development or damage to brain tissue during embryonic development and postnatally
Other chemokines showed no differences in expression between treated and control mice, CXCL4 was significantly up-regulated in the phosphate buffered saline (PBS) group, whereas human UCB (hUCB) cells showed no effects
We showed that damage to brain tissue induced changes in local chemokine expression patterns, and hUCB cell injection altered some of these patterns
Summary
Cerebral palsy (CP) is a permanent movement disorder caused by abnormal development or damage to brain tissue during embryonic development and postnatally. Chemokines have been shown to act on stem cells or damaged central nerve systems to either worsen damage or induce tissue repair [10,11,12,13]. Considering these pleiotropic functions of chemokines, it is possible that chemokines could exert therapeutic effects in treatments using UCB. We used the neonatal mouse ischemia-reperfusion (IR) brain injury model to examine chemokine expression profiles in the regionally damaged brain after tissue injury as well as after human UCB (hUCB) cell transfusion. We found that there were unique chemokine expression patterns in accordance with duration of time after brain injury (from 24 hours to 5 weeks post injury), and hUCB cells induced chemokine expression in damaged tissue
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