Volume 9 Issue 6
Nov.  2018
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Yu Xuewen, Xu Hua, Huang Zhonghua, et al. Effect of induced pluripotent stem cell transplantation on treatment of cerebral ischemic injury in rats after down-regulation of HIF-2α gene[J]. ORGAN TRANSPLANTATION, 2018, 9(6): 417-423. doi: 10.3969/j.issn.1674-7445.2018.06.004
Citation: Yu Xuewen, Xu Hua, Huang Zhonghua, et al. Effect of induced pluripotent stem cell transplantation on treatment of cerebral ischemic injury in rats after down-regulation of HIF-2α gene[J]. ORGAN TRANSPLANTATION, 2018, 9(6): 417-423. doi: 10.3969/j.issn.1674-7445.2018.06.004
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Effect of induced pluripotent stem cell transplantation on treatment of cerebral ischemic injury in rats after down-regulation of HIF-2α gene

doi: 10.3969/j.issn.1674-7445.2018.06.004

  • Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China

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  • Corresponding author: Wang Jiachuan, Email:jcwang0000@126.com
  • Received Date: 2018-08-21
    Available Online: 2021-01-19
  • Publish Date: 2018-11-15
    Abstract
  •   Objective  To investigate the effect of induced pluripotent stem cells (iPSCs) transplantation after the down-regulation of hypoxia-inducible factor (HIF)-2α gene on the treatment of cerebral ischemia injury in rats.  Methods  Twenty-four male Sprague-Dawley (SD) rats were randomly and evenly divided into the iPSCs treatment, iPSCs+siHIF-2α and phosphate buffer saline (PBS) control groups. The rat models with cerebral ischemia were established by the middle cerebral artery embolization, and reperfusion was carried out 90 min after embolization. At 3 d after reperfusion, iPSCs transplantation, iPSCs+siHIF-2α transplantation or PBS injection were performed. Before and at 2 and 4 weeks after transplantation, neurobehavioral evaluation was performed and the uptake of 18F-fluoro-deoxyglucose (18F-FDG) was measured by micro-positron emission tomography (micro-PET). At 4 weeks after transplantation, the rats were sacrificed and nerve cell markers were detected by immunofluorescence.  Results  At 2 and 4 weeks after stem cell transplantation, the neurological function scores of the iPSCs treatment group were significantly lower than those in the PBS control group (both P < 0.05), whereas the neurological function scores in the iPSCs+siHIF-2α group were considerably higher than those in the iPSCs treatment group (both P < 0.05). At 2 and 4 weeks after stem cell transplantation, the glucose metabolism levels (injured side/normal side) in the brain of cerebral ischemia rats in the iPSCs treatment and iPSCs+siHIF-2αgroups were significantly increased compared with those in the PBS control group (both P < 0.001). At the 2nd week after stem cell transplantation, the glucose metabolism level in the iPSCs treatment group was significantly higher than that in the iPSCs+siHIF-2α group (P < 0.001). Subsequently, the glucose metabolism level in the iPSCs+siHIF-2α group continued to rise until the 4th week after stem cell transplantation, which was almost identical to but still lower than that in the iPSCs treatment group (P=0.025). Immunofluorescent staining prompted that the transplanted stem cells survived and migrated to the periphery of the infarction area, and a majority of the transplanted stem cells expressed nerve cell markers.  Conclusions  iPSCs transplantation can be employed to effectively treat cerebral ischemia injury in rats. Down-regulation of HIF-2α gene exerts certain effect upon the therapeutic effect of iPSCs transplantation.

     

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    • References(17)
  • [1]
    FUJIMOTO Y, ABEMATSU M, FALK A, et al. Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell-derived long-term self-renewing neuroepithelial-like stem cells[J]. Stem Cells, 2012, 30(6): 1163-1173. DOI: 10.1002/stem.1083.
    [2]
    GLASS JD, BOULIS NM, JOHE K, et al. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase Ⅰ trial in 12 patients[J]. Stem Cells, 2012, 30(6): 1144-1151. DOI: 10.1002/stem.1079.
    [3]
    CUSIMANO M, BIZIATO D, BRAMBILLA E, et al. Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord[J]. Brain, 2012, 135(Pt 2): 447-460. DOI: 10.1093/brain/awr339.
    [4]
    AL-ZOUBI A, JAFAR E, JAMOUS M, et al. Transplantation of purified autologous leukapheresis-derived CD34+ and CD133+ stem cells for patients with chronic spinal cord injuries: long-term evaluation of safety and efficacy[J]. Cell Transplant, 2014, 23(Suppl 1): S25-S34. DOI: 10.3727/096368914X684899.
    [5]
    FELDMAN EL, BOULIS NM, HUR J, et al. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes[J]. Ann Neurol, 2014, 75(3): 363-373. DOI: 10.1002/ana.24113.
    [6]
    YANG Q, GUO M, WANG X, et al. Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance through increased extracellular adenosine levels and hypoxia-inducible factors[J]. Brain Res, 2017, 1667: 11-18. DOI: 10.1016/j.brainres.2017.04.010.
    [7]
    LI J, DONANGELO I, ABE K, et al. Thyroid hormone treatment activates protective pathways in both in vivo and in vitro models of neuronal injury[J]. Mol Cell Endocrinol, 2017, 452: 120-130. DOI: 10.1016/j.mce.2017.05.023.
    [8]
    LI QQ, SUN YP, RUAN CP, et al. Cellular prion protein promotes glucose uptake through the Fyn-HIF-2α-Glut1 pathway to support colorectal cancer cell survival[J]. Cancer Sci, 2011, 102(2): 400-406. DOI: 10.1111/j.1349-7006.2010.01811.x.
    [9]
    汪文婧, 陈旭昕, 韩志海.干细胞衰老机制及应对策略的研究进展[J].转化医学杂志, 2016, 5(4): 253-257. DOI: 10.3969/j.issn.2095-3097.2016.04.019.

    WANG WJ, CHEN XX, HAN ZH. The research progress of stem cell aging mechanisms and the solution[J]. Translat Med J, 2016, 5(4): 253-257. DOI:10.3969/j.issn.2095-3097.2016. 04.019.
    [10]
    ZHANG S, ZHAO L, WANG J, et al. HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts[J]. Cell Death Dis, 2017, 8(1): e2548. DOI: 10.1038/cddis.2016.480.
    [11]
    FENG M, ZHU H, ZHU Z, et al. Serial 18F-FDG PET demonstrates benefit of human mesenchymal stem cells in treatment of intracerebral hematoma: a translational study in a primate model[J]. J Nucl Med, 2011, 52(1): 90-97. DOI: 10.2967/jnumed.110.080325.
    [12]
    ZHANG G, CHEN L, CHEN W, et al. Neural stem cells alleviate inflammation via neutralization of IFN-γ negative effect in ischemic stroke model[J]. J Biomed Nanotechnol, 2018, 14(6): 1178-1188. DOI: 10.1166/jbn.2018.2568.
    [13]
    NGUYEN HX, HOOSHMAND MJ, SAIWAI H, et al. Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair[J]. J Neurosci, 2017, 37(38): 9269-9287. DOI: 10.1523/JNEUROSCI.2785-16.2017.
    [14]
    LI L, SALIBA P, REISCHL S, et al. Neuronal deficiency of HIF prolyl 4-hydroxylase 2 in mice improves ischemic stroke recovery in an HIF dependent manner[J]. Neurobiol Dis, 2016, 91: 221-235. DOI: 10.1016/j.nbd.2016.03.018.
    [15]
    SHELDON RA, SADJADI R, LAM M, et al. Alteration in downstream hypoxia gene signaling in neonatal glutathione peroxidase overexpressing mouse brain after hypoxia-ischemia[J]. Dev Neurosci, 2015, 37(4/5): 398-406. DOI: 10.1159/000375369.
    [16]
    DAS B, BAYAT-MOKHTARI R, TSUI M, et al. HIF-2α suppresses p53 to enhance the stemness and regenerative potential of human embryonic stem cells[J]. Stem Cells, 2012, 30(8): 1685-1695. DOI: 10.1002/stem.1142.
    [17]
    BARTECZEK P, LI L, ERNST AS, et al. Neuronal HIF-1α and HIF-2α deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke[J]. J Cereb Blood Flow Metab, 2017, 37(1): 291-306. doi: 10.1177/0271678X15624933
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