We aimed to provide an alternative cell source for cell therapy in leukoaraiosis (LA).
Methods
Olfactory ensheathing cells (OECs) from the olfactory bulb were isolated, cultured, and purified. Next, the lentivirus carrying human VEGF165 gene was constructed and transfected into OECs.
Results
The proliferative capacity of primary OECs was strong. OECs were infected with different multiplicity of infection. The expression level of VEGF was confirmed by real-time PCR with specific primers for GAPDH and VEGF, indicating that the genetically engineered OECs-VEGF produced VEGF with functional activity.
Conclusions
Our data showed that these engineered OECs-VEGF highly express functional VEGF and retain the characteristics of astrocytes and Schwann cells, providing an alternative cell source for cell therapy in LA.
LinT.C., LinY.H., KaoL.L., KaoY.H., YangY.H., ChouP.S., WuM.N.An association between the location of white matter changes and the behavioral and psychological symptoms of dementia in Alzheimer's disease patients. Transl Neurosci Clin2016, 2(1): 8–16.
2.
Sarabia-CoboC.M., PérezV., HermosillaC., NuñezM.J., de LorenaP.Apathy and leukoaraiosis in mild cognitive impairment and Alzheimer's disease: Multicenter diagnostic criteria according to the latest studies. Dement Geriatr Cogn Dis Extra2014, 4(2): 228–235.
3.
SchmidtR., RopeleS., FerroJ., MadureiraS., VerdelhoA., PetrovicK., GouwA., van der FlierW.M., EnzingerC., PantoniL.Diffusion-weighted imaging and cognition in the leukoariosis and disability in the elderly study. Stroke2010, 41(5): e402–e408.
4.
BrownW.R., ThoreC.R.Review: Cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol2011, 37(1): 56–74.
5.
DehghanianF., HojatiZ., KayM.New insights into VEGF-A alternative splicing: Key regulatory switching in the pathological process. Avicenna J Med Biotechnol2014, 6(4): 192–199.
6.
LiuF., NiJ.J., HuangJ.J., KouZ.W., SunF.Y.VEGF overexpression enhances the accumulation of phospho-S292 MeCP2 in reactive astrocytes in the adult rat striatum following cerebral ischemia. Brain Res2015, 1599: 32–43.
7.
VincentA.J., TaylorJ.M., Choi-LundbergD.L., WestA.K., ChuahM.I.Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes. Glia2005, 51(2): 132–147.
8.
Ramón-CuetoA.Olfactory ensheathing glia for nervous system repair. Exp Neurol2011, 229(1): 1.
9.
WangD.J.Why does a little mean a lot when you have nothing? A brief review of cell therapy strategies for spinal cord injury. Transl Neurosci Clin2015, 1(2): 102–109.
RousseauS., HouleF., LandryJ., HuotJ.p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene1997, 15(18): 2169–2177.
14.
McMullenM., KellerR., SussmanM., PumigliaK.Vascular endothelial growth factor-mediated activation of p38 is dependent upon Src and RAFTK/Pyk2. Oncogene2004, 23(6): 1275–1282.
Adib-SamiiP., DevanW., TraylorM., LanfranconiS., ZhangC.R., CloonanL., FalconeG.J., RadmaneshF., FitzpatrickK., KanakisA.Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. Stroke2015, 46(2): 348–353.
17.
CraftsT.D., JensenA.R., Blocher-SmithE.C., MarkelT.A.Vascular endothelial growth factor: Therapeutic possibilities and challenges for the treatment of ischemia. Cytokine2015, 71(2): 385–393.
18.
BouletiC., MathivetT., CoqueranB., SerfatyJ.M., LesageM., BerlandE., Ardidie-RobouantC., KauffensteinG., HenrionD., LapergueB.Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke. Eur Heart J2013, 34(47): 3657–3668.
19.
GrueterB.E., SchulzU.G.Age-related cerebral white matter disease (leukoaraiosis): A review. Postgrad Med J2012, 88(1036): 79–87.
20.
EkbergJ.A.K., St JohnJ.A.Crucial roles for olfactory ensheathing cells and olfactory mucosal cells in the repair of damaged neural tracts. Anat Rec2014, 297(1): 121–128.
21.
BartolomeiJ.C., GreerC.A.Olfactory ensheathing cells: Bridging the gap in spinal cord injury. Neurosurgery2000, 47(5): 1057–1069.
22.
MouhieddineT.H., KobeissyF.H., ItaniM., NokkariA., WangK.K.W.Stem cells in neuroinjury and neurodegenerative disorders: Challenges and future neurotherapeutic prospects. Neural Regen Res2014, 9(9): 901–906.
