Human umbilical cord mesenchymal stem cells inhibit the proliferation of peripheral blood mononuclear cells in Parkinson’s disease patients

doi:10.3969/j.issn.1006-7795.2014.03.016

Abstract

Abstract:

Objective To observe the immune-suppression ability of umbilical cord mesenchymal stem cells(UC-MSC) on the proliferation of peripheral blood mononuclear cells(PBMC), which were isolated from young(25~35 years) healthy, middle aged(50~60 years) healthy, and middle aged PD(Parkinson's disease) individuals and to explore what cytokines are required to induce UC-MSC to be immune-suppressive. Methods All the recruits were males. Co-culture of the PBMCs and the UC-MSC pretreated by different cytokines and measure the proliferation of PBMC were done. Results The immune-suppression ability of UC-MSC was confirmed with young healthy, middle aged healthy, and middle aged PD individuals. In our experiments, IFN-γ synergized with TNFα, IL-1α, or IL-1β in inducing UC-MSCs was proved to inhibit PBMC proliferation. The combinations of "IFN-γ+IL-1α" and "IFN-α+IL-1β" are more powerful than "IFN-γ+TNF-α" in inducing UC-MSC to inhibit the proliferation of PBMC. We also found that the PBMC proliferation of young after UC-MSC co-culture was significantly lower than that of PD patients, but the proliferation of PD patients' PBMC didn't show any difference when compared with middle aged healthy ones. Conclusions All of these results showed that the immune-suppression ability of UC-MSC is not innate, but is cytokine stimulation dependent. Furthermore, the PBMC inhibition of PD patient, together with that the PD progression did not affect the response of PBMC toward the inhibition of UC-MSC, is the direct evidence that UC-MSC might be a candidate cell type in anti-inflammation therapy of PD.

Key words: umbilical cord, mesenchymal stem cells, Parkinson’s disease, inflammation, transplantation

CLC Number:

R741

Zhao Chunsong, Zou Haiqiang, Yan Xiaoming, Guan Yunqian, Chen Ling, Wang Jiayin, Zhang Yu. Human umbilical cord mesenchymal stem cells inhibit the proliferation of peripheral blood mononuclear cells in Parkinson’s disease patients[J]. Journal of Capital Medical University, 2014, 35(3): 344-352.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2014.03.016

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2014/V35/I3/344

References

[1] Hirsch E C, Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection?[J]. Lancet Neurol, 2009, 8(4):382-397.
[2] Tansey M G, Goldberg M S. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention[J]. Neurobiol Dis, 2010, 37(3):510-518.
[3] McGeer P L, Itagaki S, Boyes B E, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains[J]. Neurology, 1988, 38(8):1285-1291.
[4] Ouchi Y, Yoshikawa E, Sekine Y, et al. Microglial activation and dopamine terminal loss in early Parkinson's disease[J]. Ann Neurol, 2005, 57(2):168-175.
[5] Long-Smith C M, Sullivan A M, Nolan Y M. The influence of microglia on the pathogenesis of Parkinson's disease[J]. Prog Neurobiol, 2009, 89(3):277-287.
[6] Marinova-Mutafchieva L, Sadeghian M, Broom L, et al. Relationship between microglial activation and dopaminergic neuronal loss in the substantia nigra: a time course study in a 6-hydroxydopamine model of Parkinson's disease[J]. J Neurochem, 2009, 110(3):966-975.
[7] Arimoto T, Choi D Y, Lu X, et al. Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra[J]. Neurobiol Aging, 2007, 28(6):894-906.
[8] Feng Z H, Wang T G, Li D D, et al. Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl 1, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra[J]. Neurosci Lett, 2002, 329(3):354-358.
[9] Vijitruth R, Liu M, Choi D Y, et al. Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease[J]. J Neuroinflammation, 2006, 3:6.
[10] Liberatore G T, Jackson-Lewis V, Vukosavic S, et al. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease[J]. Nat Med, 1999, 5(12):1403-1409.
[11] Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells[J]. Lancet, 2004, 363(9419):1439-1441.
[12] Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versushost disease: a phase Ⅱ study[J]. Lancet, 2008, 371(9624):1579——1586.
[13] Di Nicola M, Carlo-stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli[J]. Blood, 2002, 99(10):3838-3843.
[14] Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions[J]. Blood, 2006, 107(1):367-372.
[15] Spaggiari G M, Capobianco A, Abdelrazik H, et al. Mesenchymal stem cells inhibit natural killer cell proliferation, cytotoxicity and cytokine production: role of indoleamine 2, 3-dioxygenase and prostaglandin E2[J]. Blood, 2008, 111(3):1327-1333.
[16] 寿培舜, 黄寅, 苏娟娟, 等.间充质干细胞免疫抑制机制及在疾病中的应用[J].细胞生物学杂志, 2009, 31(1):15-20.
[17] 王晓辉, 罗芸, 贾庆华, 等.Notch1对人脐带间充质干细胞增殖、黏附及迁移影响的体外研究[J].解放军医药杂志, 2013, 25(10):16-21.
[18] Yoo K H, Jang I K, Lee M W, et al. Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues[J]. Cell Immunol, 2009, 259(2):150-156.
[19] Hughes A J, Daniel S E, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases[J].J Neurol Neurosurg Psychiatry, 1992, 55(3):181-184.
[20] Asanuma M, Miyazaki I. Common anti-inflammatory drugs are potentially therapeutic for Parkinson's disease?[J]. Exp Neurol, 2007, 206(2):172-178.
[21] Samii A, Etminan M, Wiens M O, et al. NSAID use and the risk of Parkinson's disease: systematic review and meta-analysis of observational studies[J]. Drugs Aging, 2009, 26(9):769-779.
[22] Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide[J]. Cell Stem Cell, 2008, 2(2):141-150.