Comparison of TGF-β and Nitric Oxide Production by Adipose-Derived Mesenchymal Stem Cells Between Healthy Pregnant and Preeclamptic Women

Document Type : Original Article

Authors

1 Immunoregulation Research Center, Shahed University, Tehran, Iran.

2 Immunoregulation Research Center, Shahed University, Tehran, Iran Department of Gynecology, Shahed University, Tehran, Iran

3 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Immunology, Faculty of Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Background: Preeclampsia is one of the most common complications of pregnancy that occurs after the 20th weeks of pregnancy. The pathophysiology of this disease is not exactly known. Transforming Growth Factor-Beta (TGF-β) and Nitric Oxide (NO) are the key regulatory factors secreted by Mesenchymal Stem Cells (MSCs). The aim of the present study was to evaluate the TGF-β and NO secretion by adipose-derived MSCs in normal and preeclamptic pregnant women.
Materials and Methods: The adipose tissues were collected from 10 preeclamptic patients and 10 age-matched normotensive controls at the time of cesarean section delivery. After isolation and expansion of MSCs, their capability of differentiation and immunophenotyping characteristics were assessed. Next, the release of TGF-ß was evaluated making use of ELISA sandwich method and Griess method was used to measure the level of NO.
Results: Adipose derived MSCs in both groups were differentiated into osteocytes and adipocytes. The expression of CD90, CD73, CD44, and CD105 markers and lack of expression of CD-14, CD34, CD45, and HLA-DR markers in cells isolated from adipose in both groups was observed using flow cytometric analysis. The levels of TGF-ß secretion in preeclamptic women were significantly higher than those in control group, but the mean level of NO secreted by adipose derived MSCs did not significantly change in the two groups.
Conclusion: It can be concluded that significant increase in the secretion of TGF-β owing to MSCs in preeclamptic participants shows the importance of these cells in controlling immunological balance in these patients. Therefore, MSCs-based therapy seems to regulate TH1/Th2 balance in preeclampsia.

Keywords

References

Stennett AK, Khalil RA. Neurovascular mechanisms of hypertension in pregnancy. Current Neurovascular Research. 2006; 3(2):131-48. [DOI:10.2174/156720206776875885]
Petrozella L, Mahendroo M, Timmons B, Roberts S, McIntire D, Alexander JM. Endothelial microparticles and the antiangiogenic state in preeclampsia and the postpartum period. American Journal of Obstetrics and Gynecology. 2012; 207(2):140.e20-e26.
Cerdeira AS, Karumanchi SA. Angiogenic factors in preeclampsia and related disorders. Cold Spring Harbor Perspectives in Medicine. 2012; 2(11):a006585. [DOI:10.1101/cshperspect.a006585] [PMID] [PMCID]
Lorquet S, Pequeux C, Munaut C, Foidart J-M. Aetiology and physiopathology of preeclampsia and related forms. Acta Clinica Belgica. 2010; 65(4):237-41. [DOI:10.1179/acb.2010.051] [PMID]
Gilbert ES. Manual of high risk pregnancy and delivery. London: Elsevier Health Sciences; 2010.
Mustafa R, Ahmed S, Gupta A, Venuto RC. A comprehensive review of hypertension in pregnancy. Journal of pregnancy. 2012;2012.
Schaaps JP, Tsatsaris V, Goffin F, Brichant JF, Delbecque K, Tebache M, et al. Shunting the intervillous space: New concepts in human uteroplacental vascularization. American Journal of Obstetrics and Gynecology. 2005; 192(1):323-32. [DOI:10.1016/j.ajog.2004.06.066] [PMID]
Rolfo A, Giuffrida D, Nuzzo AM, Pierobon D, Cardaropoli S, Piccoli E, et al. Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia. PloS One. 2013; 8(3):e59403. [DOI:10.1371/journal.pone.0059403] [PMID] [PMCID]
Parolini O, Alviano F, Bergwerf I, Boraschi D, De Bari C, De Waele P, et al. Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table. Stem Cells and Development. 2010; 19(2):143-54. [DOI:10.1089/scd.2009.0404] [PMID]
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Engineering. 2001; 7(2):211-28. [DOI:10.1089/107632701300062859] [PMID]
Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004; 22(4):625-34. [DOI:10.1634/stemcells.22-4-625] [PMID]
Kögler G, Sensken S, Airey JA, Trapp T, Müschen M, Feldhahn N, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. The Journal of Experimental Medicine. 2004; 200(2):123-35. [DOI:10.1084/jem.20040440] [PMID] [PMCID]
Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Research. 2000; 2(6):477-88. [DOI:10.1186/ar130] [PMID] [PMCID]
Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta‐derived cells have mesenchymal stem/progenitor cell potential. Stem Cells. 2004;22(5):649-58. [DOI:10.1634/stemcells.22-5-649] [PMID]
Lee JM, Jung J, Lee H-J, Jeong SJ, Cho KJ, Hwang S-G, et al. Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells. International Immunopharmacology. 2012; 13(2):219-24. [DOI:10.1016/j.intimp.2012.03.024] [PMID]
Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell stem cell. 2008; 2(2):141-50. [DOI:10.1016/j.stem.2007.11.014] [PMID]
Han Z, Jing Y, Zhang S, Liu Y, Shi Y, Wei L. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth. Cell & Bioscience. 2012; 2(1):8. [DOI:10.1186/2045-3701-2-8] [PMID] [PMCID]
Ghannam S, Bouffi C, Djouad F, Jorgensen C, Noël D. Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications. Stem cell research & therapy. 2010; 1(1):2. [DOI:10.1186/scrt2] [PMID] [PMCID]
Bassi ÊJ, Aita CAM, Câmara NOS. Immune regulatory properties of multipotent mesenchymal stromal cells: Where do we stand? World journal of stem cells. 2011;3(1):1. [DOI:10.4252/wjsc.v3.i1.1] [PMID] [PMCID]
Mansouri R, Akbari F, Vodjgani M, Mahboudi F, Kalantar F, Mirahmadian M. Serum cytokines profiles in Iranian patients with preeclampsia. Iranian Journal of Immunology. 2007; 4(3):179-85. [PMID]
Obstetricians ACo, Gynecologists. Diagnosis and management of preeclampsia and eclampsia. ACOG practice bulletin. 2002; 33:159-67.
Bunnell BA, Flaat M, Gagliardi C, Patel B, Ripoll C. Adipose-derived stem cells: isolation, expansion and differentiation. Methods. 2008; 45(2):115-20. [DOI:10.1016/j.ymeth.2008.03.006] [PMID] [PMCID]
Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Experimental hematology. 2005; 33(11):1402-16. [DOI:10.1016/j.exphem.2005.07.003] [PMID]
Bassi ÊJ, de Almeida DC, Moraes-Vieira PMM, Câmara NOS. Exploring the role of soluble factors associated with immune regulatory properties of mesenchymal stem cells. Stem Cell Reviews and Reports. 2012; 8(2):329-42. [DOI:10.1007/s12015-011-9311-1] [PMID]
Liu F, Jiang N, Xiao ZY, Cheng JP, Mei YZ, Zheng P, et al. Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo. PeerJ. 2016; 4:e1890. [DOI:10.7717/peerj.1890] [PMID] [PMCID]
Batal M, Boudry I, Mouret S, Cléry-Barraud C, Wartelle J, Bérard I, et al. DNA damage in internal organs after cutaneous exposure to sulphur mustard. Toxicology andApplied Pharmacology. 2014; 278(1):39-44. [DOI:10.1016/j.taap.2014.04.003] [PMID]
Ghanei M, Poursaleh Z, Harandi AA, Emadi SE, Emadi SN. Acute and chronic effects of sulfur mustard on the skin: a comprehensive review. Cutaneous and Ocular Toxicology. 2010; 29(4):269-77. [DOI:10.3109/15569527.2010.511367] [PMID]
Zhao ZG, Cao Z, Xu W, Sun L, You Y, Li F, et al. Immune protection function of multipotent mesenchymal stromal cells: role of transforming growth factor-β1. Cancer investigation. 2012; 30(9):646-56. [DOI:10.3109/07357907.2012.721038] [PMID]
Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA. Transforming growth factor-β regulation of immune responses. Annual Review of Immunology. 2006; 24:99-146. [DOI:10.1146/annurev.immunol.24.021605.090737] [PMID]
Liu L, Zhao G, Fan H, Zhao X, Li P, Wang Z, et al. Mesenchymal stem cells ameliorate Th1-induced pre-eclampsia-like symptoms in mice via the suppression of TNF-α expression. PLoS One. 2014; 9(2):e88036. [DOI:10.1371/journal.pone.0088036] [PMID] [PMCID]
Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007; 109(1):228-34. [DOI:10.1182/blood-2006-02-002246] [PMID]
Kukor Z, Valent S. Nitric oxide and preeclampsia. Orvosi hetilap. 2010; 151(52):2125-35. [DOI:10.1556/OH.2010.29012] [PMID]
Groesch KA, Torry RJ, Wilber AC, Abrams R, Bieniarz A, Guilbert LJ, et al. Nitric oxide generation affects pro-and anti-angiogenic growth factor expression in primary human trophoblast. Placenta. 2011; 32(12):926-31. [DOI:10.1016/j.placenta.2011.08.008] [PMID] [PMCID]
Shaamash A, Elsnosy E, Makhlouf A, Zakhari M, Ibrahim O, El-Dien H. Maternal and fetal serum Nitric Oxide (NO) concentrations in normal pregnancy, pre-eclampsia and eclampsia. International Journal of Gynecology & Obstetrics. 2000; 68(3):207-14. [DOI:10.1016/S0020-7292(99)00213-1]
Anumba DO, Robson SC, Boys RJ, Ford GA. Nitric oxide activity in the peripheral vasculature during normotensive and preeclamptic pregnancy. American Journal of Physiology-Heart and Circulatory Physiology. 1999; 277(2):H848-H54. [DOI:10.1152/ajpheart.1999.277.2.H848] [PMID]
Venkatesha S, Toporsian M, Lam C, Hanai JI, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nature Medicine. 2006; 12(6):642-9. [DOI:10.1038/nm1429] [PMID]
Conley BA, Koleva R, Smith JD, Kacer D, Zhang D, Bernabéu C, et al. Endoglin controls cell migration and composition of focal adhesions function of the cytosolic domain. Journal of Biological Chemistry. 2004; 279(26):27440-9. [DOI:10.1074/jbc.M312561200] [PMID]
Das U. Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension. European Journal of Clinical Nutrition. 2004; 58(2):195-203. [DOI:10.1038/sj.ejcn.1601766] [PMID]
Anton L, Merrill DC, Neves L, Gruver C, Moorefield C, Brosnihan KB. Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: An in vitro study. Reprod Biol Endocrinol. 2010; 8:135. [DOI:10.1186/1477-7827-8-135] [PMID] [PMCID]
Immunoregulation
Volume 1, Issue 1 - Serial Number 1
Summer & Autumn
July 2018
Pages 11-20

Files

Share

How to cite

Statistics