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Effect of Human Umbilical Cord Mesenchymal Stem Cell Transplantation in a Rat Model of Preeclampsia

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Abstract

Objective

To test the effects of human umbilical cord mesenchymal stem cell (HU-MSC) transplantation on reversing preeclampsia (PE) symptoms in a lipopolysaccharide (LPS)-induced rat PE model.

Methods

Human umbilical cord MSCs were detected, isolated, and cultured. Human umbilical cord MSC transplantation was conducted. Expressions of inflammatory cytokines in serum and placental tissue were measured by enzyme-linked immunosorbent assay. Changes in inflammatory cytokines, peroxisome proliferator-activated receptor γ (PPARγ), laminin receptor 1 (LR1), matrix metalloproteinase (MMP) 2, and MMP-9 messenger RNA (mRNA) levels in placental tissue were recorded by quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blotting were performed for PPARγ detection.

Results

The LPS group exhibited increased blood pressure and proteinuria and decreased fetal weight compared to the normal pregnancy (NP) group (all P < .05). The LPS + MSC group presented lowered blood pressure and higher fetal weight than the LPS group (P < .05). The levels of interferon γ, tumor necrosis factor α (TNF-α), interleukin (IL) 1β, IL-6, IL-8, IL-12, and intercellular adhesion molecule 1 (ICAM-1) increased and the levels of IL-4 and IL-10 levels decreased in the LPS group compared to the NP group (all P < .05). Tumor necrosis factor α, IL-6, IL-12, and ICAM-1 levels decreased and IL-10 level increased in the LPS + MSC group compared to the LPS group (all P < .05). The LPS-MSC group showed lower mRNA expressions of TNF-α, IL-6, MMP-2, MMP-9, and ICAM-1 and higher mRNA expressions of IL-10, PPARγ, and LR1 than the LPS group (all P < .05).

Conclusion

In summary, HU-MSC transplantation may be extremely beneficial for PE therapy.

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References

  1. Too GT, Hill JB. Hypertensive crisis during pregnancy and postpartum period. Semin Perinatol. 2013;37(4):280–287.

    PubMed  Google Scholar 

  2. Solomon CG, Seely EW. Hypertension in pregnancy. Endocrinol Metab Clin North Am. 2011;40(4):847–863.

    CAS  PubMed  Google Scholar 

  3. Maloney KF, Heller D, Baergen RN. Types of maternal hypertensive disease and their association with pathologic lesions and clinical factors. Fetal Pediatr Pathol. 2012;31(5):319–323.

    PubMed  Google Scholar 

  4. Arulkumaran N, Lightstone L. Severe pre-eclampsia and hypertensive crises. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):877–884.

    CAS  PubMed  Google Scholar 

  5. Kim JS, Kang EJ, Woo OH, et al. The relationship between preeclampsia, pregnancy-induced hypertension and maternal risk of breast cancer: a meta-analysis. Acta Oncol. 2013;52(8):1643–1648.

    PubMed  Google Scholar 

  6. Fu B, Tian Z, Wei H. TH17 cells in human recurrent pregnancy loss and pre-eclampsia. Cell Mol Immunol. 2014;11(6):564–570.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Barakonyi A, Miko E, Szereday L, et al. Cell death mechanisms and potentially cytotoxic natural immune cells in human pregnancies complicated by preeclampsia. Reprod Sci. 2014;21(2):155–166.

    PubMed  Google Scholar 

  8. Tayal D, Goswami B, Patra SK, Tripathi R, Khaneja A. Association of inflammatory cytokines, lipid peroxidation end products and nitric oxide with the clinical severity and fetal outcome in preeclampsia in Indian women. Indian J Clin Biochem. 2014;29(2):139–144.

    CAS  PubMed  Google Scholar 

  9. Ferguson KK, McElrath TF, Chen YH, Mukherjee B, Meeker JD. Longitudinal profiling of inflammatory cytokines and C-reactive protein during uncomplicated and preterm pregnancy. Am J Reprod Immunol. 2014;72(3):326–336.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Jain A, Schneider H, Aliyev E, et al. Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response. Lab Invest. 2014;94(8):873–880.

    CAS  PubMed  Google Scholar 

  11. Geifman-Holtzman O, Xiong Y, Holtzman EJ. Gadd45 stress sensors in preeclampsia. Adv Exp Med Biol. 2013;793:121–129.

    CAS  PubMed  Google Scholar 

  12. Castro-Manrreza ME, Mayani H, Monroy-Garcia A, et al. Human mesenchymal stromal cells from adult and neonatal sources: a comparative in vitro analysis of their immunosuppressive properties against T cells. Stem Cells Dev. 2014;23(11):1217–1232.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Veryasov VN, Savilova AM, Buyanovskaya OA, Chulkina MM, Pavlovich SV, Sukhikh GT. Isolation of mesenchymal stromal cells from extraembryonic tissues and their characteristics. Bull Exp Biol Med. 2014;157(1):119–124.

    CAS  PubMed  Google Scholar 

  14. El Omar R, Beroud J, Stoltz JF, Menu P, Velot E, Decot V. Umbilical cord mesenchymal stem cells: the new gold standard for mesenchymal stem cell-based therapies?. Tissue Eng Part B Rev. 2014;20(5):523–544.

    PubMed  Google Scholar 

  15. Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica. 2006;91(8):1017–1026.

    CAS  PubMed  Google Scholar 

  16. De Schauwer C, Goossens K, Piepers S, et al. Characterization and profiling of immunomodulatory genes of equine mesenchymal stromal cells from non-invasive sources. Stem Cell Res Ther. 2014;5(1):6.

    PubMed  PubMed Central  Google Scholar 

  17. Karlupia N, Manley NC, Prasad K, Schafer R, Steinberg GK. Intra-arterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model. Stem Cell Res Ther. 2014;5(2):45.

    PubMed  PubMed Central  Google Scholar 

  18. Joerger-Messerli M, Bruhlmann E, Bessire A, et al. Preeclampsia enhances neuroglial marker expression in umbilical cord Wharton’s jelly-derived mesenchymal stem cells. J Matern Fetal Neonatal Med. 2015;28(4):464–469.

    CAS  PubMed  Google Scholar 

  19. Wang Y, Fan H, Zhao G, et al. miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. FEBS J. 2012;279(24):4510–4524.

    CAS  PubMed  Google Scholar 

  20. Liu L, Zhao G, Fan H, et al. Mesenchymal stem cells ameliorate Th1-induced pre-eclampsia-like symptoms in mice via the suppression of TNF-alpha expression. PLoS One. 2014;9(2):e88036.

    PubMed  PubMed Central  Google Scholar 

  21. Nuzzo AM, Giuffrida D, Zenerino C, et al. JunB/Cyclin-D1 imbalance in placental mesenchymal stromal cells derived from preeclamptic pregnancies with fetal-placental compromise. Placenta. 2014;35(7):483–490.

    CAS  PubMed  Google Scholar 

  22. Liu L, Wang Y, Fan H, et al. MicroRNA-181a regulates local immune balance by inhibiting proliferation and immunosuppressive properties of mesenchymal stem cells. Stem Cells. 2012;30(8):1756–1770.

    CAS  PubMed  Google Scholar 

  23. Yan Y, Xu W, Qian H, et al. Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo. Liver Int. 2009;29(3):356–365.

    CAS  PubMed  Google Scholar 

  24. Qiao CXW, Zhu W, Hu J, Qian H, Yin Q. Human mesenchymal stem cells isolated from the umbilical cord. Cell Biol Int. 2008;32(1):8–15.

    CAS  PubMed  Google Scholar 

  25. Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis. Liver Transpl. 2009;15(5):484–495.

    PubMed  Google Scholar 

  26. Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and Trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension. 2013;62(6):1046–1054.

    CAS  PubMed  Google Scholar 

  27. Laresgoiti-Servitje E. A leading role for the immune system in the pathophysiology of preeclampsia. J Leukoc Biol. 2013;94(2):247–257.

    CAS  PubMed  Google Scholar 

  28. James MT, Hemmelgarn BR, Wiebe N, et al. Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet. 2010;376(9758):2096–2103.

    PubMed  Google Scholar 

  29. Hamilton S, Oomomian Y, Stephen G, et al. Macrophages infiltrate the human and rat decidua during term and preterm labor: evidence that decidual inflammation precedes labor. Biol Reprod. 2012;86(2):39.

    PubMed  Google Scholar 

  30. Ryu M, Migliorini A, Miosge N, et al. Plasma leakage through glomerular basement membrane ruptures triggers the proliferation of parietal epithelial cells and crescent formation in noninflammatory glomerular injury. J Pathol. 2012;228(4):482–494.

    CAS  PubMed  Google Scholar 

  31. Rutland CS, Atkinson SD, Mukhopadhyay M, et al. Thrombophilic-type placental pathologies and skeletal growth delay following maternal administration of angiostatin4.5 in mice. Biol Reprod. 2011;84(3):505–513.

    CAS  PubMed  Google Scholar 

  32. Roberts DJ. New hope for prevention of preterm delivery. Am J Pathol. 2013;183(2):330–332.

    PubMed  Google Scholar 

  33. Zhu HL, Liu YL, Xie XL, Huang JJ, Hou YQ. Effect of L-arginine on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge. Innate Immun. 2013;19(3):242–252.

    CAS  PubMed  Google Scholar 

  34. Monz D, Tutdibi E, Mildau C, et al. Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. PLoS One. 2013;8(9):e74740.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Vonlaufen A, Phillips PA, Xu Z, et al. Withdrawal of alcohol promotes regression while continued alcohol intake promotes persistence of LPS-induced pancreatic injury in alcohol-fed rats. Gut. 2011;60(2):238–246.

    CAS  PubMed  Google Scholar 

  36. Zhang MJ, Sun JJ, Qian L, et al. Human umbilical mesenchymal stem cells enhance the expression of neurotrophic factors and protect ataxic mice. Brain Res. 2011;1402:122–131.

    CAS  PubMed  Google Scholar 

  37. Zhang Z, Dai M. Effect of paeonol on adhesive function of rat vascular endothelial cells induced by lipopolysaccharide and cocultured with smooth muscle cells. Zhongguo Zhong Yao Za Zhi. 2014;39(6):1058–1063.

    CAS  PubMed  Google Scholar 

  38. Adams WJ, Zhang Y, Cloutier J, et al. Functional vascular endothelium derived from human induced pluripotent stem cells. Stem Cell Reports. 2013;1(2):105–113.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Rautou PE, Leroyer AS, Ramkhelawon B, et al. Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circ Res. 2011;108(3):335–343.

    CAS  PubMed  Google Scholar 

  40. Munro SK, Mitchell MD, Ponnampalam AP. Histone deacetylase inhibition by trichostatin A mitigates LPS induced TNFalpha and IL-10 production in human placental explants. Placenta. 2013;34(7):567–573.

    CAS  PubMed  Google Scholar 

  41. Brewster JA, Orsi NM, Gopichandran N, Ekbote UV, Cadogan E, Walker JJ. Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model. Hypertens Pregnancy. 2008;27(1):1–16.

    CAS  PubMed  Google Scholar 

  42. Brewster JA, Orsi NM, Gopichandran N, McShane P, Ekbote UV, Walker JJ. Gestational effects on host inflammatory response in normal and pre-eclamptic pregnancies. Eur J Obstet Gynecol Reprod Biol. 2008;140(1):21–26.

    PubMed  Google Scholar 

  43. Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007;262(5):509–525.

    PubMed  Google Scholar 

  44. Lisianyi MI. Mesenchymal stem cells and their immunological properties. Fiziol Zh. 2013;59(3):126–134.

    CAS  PubMed  Google Scholar 

  45. Kode JA, Mukherjee S, Joglekar MV, Hardikar AA. Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy. 2009;11(4):377–391.

    CAS  PubMed  Google Scholar 

  46. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–1822.

    CAS  PubMed  Google Scholar 

  47. Rasmusson I, Ringden O, Sundberg B, Le Blanc K. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res. 2005;305(1):33–41.

    CAS  PubMed  Google Scholar 

  48. Higdon A, Diers AR, Oh JY, Landar A, Darley-Usmar VM. Cell signalling by reactive lipid species: new concepts and molecular mechanisms. Biochem J. 2012;442(3):453–464.

    CAS  PubMed  Google Scholar 

  49. Waku T, Shiraki T, Oyama T, et al. Structural insight into PPAR-gamma activation through covalent modification with endogenous fatty acids. J Mol Biol. 2009;385(1):188–199.

    CAS  PubMed  Google Scholar 

  50. Rustveld LO, Kelsey SF, Sharma R. Association between maternal infections and preeclampsia: a systematic review of epidemiologic studies. Matern Child Health J. 2008;12(2):223–242.

    PubMed  Google Scholar 

  51. Kim S, Choi JH, Kim JB, et al. Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells. Molecules. 2008;13(12):2975–2985.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Adya R, Tan BK, Chen J, Randeva HS. Nuclear factor-kappaB induction by visfatin in human vascular endothelial cells: its role in MMP-2/9 production and activation. Diabetes Care. 2008;31(4):758–760.

    CAS  PubMed  Google Scholar 

  53. Kurdoglu M, Kurdoglu Z, Ozen S, et al. Expression of laminin receptor 1 in human placentas from normal and preeclamptic pregnancies and its relationship with the severity of preeclampsia. J Perinat Med. 2011;39(4):411–416.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, 110004, Shenyang, PR China

    Lei-Lei Wang MD, Yang Yu MD, Hong-Bo Guan MD & Chong Qiao MD

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  1. Lei-Lei Wang MD
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  2. Yang Yu MD
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  3. Hong-Bo Guan MD
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  4. Chong Qiao MD
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Correspondence to Chong Qiao MD.

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Wang, LL., Yu, Y., Guan, HB. et al. Effect of Human Umbilical Cord Mesenchymal Stem Cell Transplantation in a Rat Model of Preeclampsia. Reprod. Sci. 23, 1058–1070 (2016). https://doi.org/10.1177/1933719116630417

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