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. 2020 May;80(3):247-256.
doi: 10.1002/jdn.10021. Epub 2020 Mar 25.

Elevation of stromal cell-derived factor 1 and C-X-C chemokine receptor type 4 in white matter damage treatment with recombinant human erythropoietin and human umbilical cord mesenchymal stem cells in a rat model of preterm birth

Liping Yin  1   2 , Shiyu Wang  3 , Ning Zhang  1   2 , Xiang Bai  4 , Jiali Xie  1   2 , Quan Wen  1   2 , Li Huang  1   2 , Lijuan Qian  1   2 , Li Jiang  1   2
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Elevation of stromal cell-derived factor 1 and C-X-C chemokine receptor type 4 in white matter damage treatment with recombinant human erythropoietin and human umbilical cord mesenchymal stem cells in a rat model of preterm birth

Liping Yin et al. Int J Dev Neurosci. 2020 May.

Abstract

Objectives: To investigate the role of stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) in the premature brain with white matter damage (WMD) undergoing treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) and recombinant human erythropoietin (rhEPO).

Experimental design: Three-day-old Sprague-Dawley (SD) rats were randomly divided into sham operation group, hypoxia-ischemia (HI) group, rhEPO treated HI group, hUC-MSCs treated HI group, and rhEPO + hUC-MSCs treated HI group. WMD was established in all groups except the Sham group. SDF-1 and CXCR-4 levels in each group were detected at postnatal day (P) 5, P7, and P14. Pathological changes were assessed via HE staining at P14 and neuroethological tests were performed at P28.

Observations and conclusions: The rhEPO and hUC-MSCs intervention reduced injury area, increased body weight at P7, and improved neurobehavioral scores at P28. Furthermore, their combined use proved even more beneficial. SDF-1 levels in the rhEPO group were higher than those in the other groups and highest in the hUC-MSCs + rhEPO group (all p < .01). SDF-1 levels in the hUC-MSCs + rhEPO and rhEPO groups were increased at P5 and reached a peak at P7. CXCR-4 levels in the hUC-MSCs group were higher than those in the other groups and highest in the hUC-MSCs + rhEPO group (all p < .01). CXCR-4 levels were also increased at P5 and highest at P14.

Significance: hUC-MSCs + rhEPO might reduce nerve cell damage and improve neurobehavioral development, in connection with increased SDF-1 and CXCR-4 expression, in premature rats with WMD due to hypoxic-ischemic injury.

Keywords: CXC family chemokine 4; human umbilical cord mesenchymal stem cells; hypoxia-ischemia; premature rats; recombinant human erythropoietin; stromal cell-derived factor 1; white matter damage.

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