CONDITIONED MEDIA OF MESENCHYMAL STEM CELLS RECOVERS PLACENTAL GROWTH FACTOR IN PRISTANE MICE MODEL
DOI:
https://doi.org/10.22159/ajpcr.2019.v12i10.35198Keywords:
Conditioned media, Mesenchymal stem cells, Placental growth factorAbstract
Objectives: A low level of placental growth factor (PlGF) expression in placenta is strongly correlated with pregnancy loss, prematurity, fetal growth restriction, and preeclampsia. Pristane-induced lupus in mice model has been widely used to present placental damage and poor pregnancy outcomes. Conditioned media (CM), which is medium for culturing mesenchymal stem cells (MSCs), have grown much attention recently. It has rich amount of growth factors, exosomes, microvesicles, and immunomodulatory molecules. These could become beneficial resources to recover poor placentation.
Methods: CM taken from the 3rd to 4th passage of the culture were underdone by using explant method of human umbilical cord (hUC). Ninety BALB/c mice were randomly distributed into three groups: Normal, pristane, and pristane + CM group. Mice in normal group were injected with 0.5 ml normal saline and other groups with 0.5 ml pristane. Four weeks later, mice were mated and only pristane + CM group received therapy of CM-MSCs 0.5 ml single dose after pregnancy was confirmed. On day 16, pregnancy was terminated and the placenta was analyzed for PlGF expression using immunoreactive score and statistically tested with analysis of variance.
Results: The average of PlGF expression in normal, pristane, and pristane + CM group was 9.528, 3.428, and 10.085, respectively. CM have significantly increase PlGF (p<0.01**) and equal to normal (p=0.301).
Conclusion: CM of hUC-MSCs has shown its therapeutical effect among the low level of PlGF in damaged placenta, and potentially would prevent fetal growth restriction and preeclampsia arose from spiral artery remodeling failure.
Downloads
References
Kim MY, Buyon JP, Guerra MM, Rana S, Zhang D, Laskin CA, et al. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: Results of the PROMISSE study. Am J Obstet Gynecol 2016;214:108.
Selvaraj LR, Rose N, Ramachandran M. First trimester screening for pre-eclampsia and fetal growth restriction. J Fetal Med 2016;3:77-84.
Chaiworapongsa T, Romero R, Korzeniewski SJ, Kusanovic JP, Soto E, Lam J, et al. Maternal plasma concentrations of angiogenic/ antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia. Am J Obstet Gynecol 2013;208:287.e1-.87E+17.
Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci 2017;18:1852.
Ferreira JR, Teixeira GQ, Santos SG, Barbosa MA, Almeida-Porada G, Gonçalves RM, et al. Mesenchymal stromal cell secretome: Influencing therapeutic potential by cellular pre-conditioning. Front Immunol 2018;9:2837.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: The arrive guidelines for reporting animal research. Animals 2013;4:35-44.
Smith AJ, Clutton RE, Lilley E, Hansen KEA, Brattelid T. PREPARE:Guidelines for planning animal research and testing. Lab Anim 2018;52:135-41.
Pawitan J, Liem I, Budiyanti E. Umbilical cord derived stem cell culture: Multiple-harvest explant method. Int J PharmTech Res 2014;6:1202-8.
Pawitan J, Kispa T, Mediana D, Goei N, Fasha I, Liem I, et al. Simple production method of umbilical cord derived mesenchymal stem cell using xeno-free materials for translational research. J Chem Pharm Res 2015;7:652-6.
Redman CW, Staff AC. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. Am J Obstet Gynecol 2015;213:S9.e1, S9-11.
Kuroda Y, Akaogi J, Nacionales DC, Wasdo SC, Szabo NJ, Reeves WH, et al. Distinctive patterns of autoimmune response induced by different types of mineral oil. Toxicol Sci 2004;78:222-8.
Reeves WH, Lee PY, Weinstein JS, Satoh M, Lu L. Induction of autoimmunity by pristane and other naturally occurring hydrocarbons. Trends Immunol 2009;30:455-64.
Calvani N, Caricchio R, Tucci M, Sobel ES, Silvestris F, Tartaglia P, et al. Induction of apoptosis by the hydrocarbon oil pristane: Implications for pristane-induced lupus. J Immunol 2005;175:4777-82.
Satoh M, Reeves WH. Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane. J Exp Med 1994;180:2341-6.
Clynes R, Calvani N, Croker BP, Richards HB. Modulation of the immune response in pristane-induced lupus by expression of activation and inhibitory fc receptors. Clin Exp Immunol 2005;141:230-7.
Cetin I, Mazzocco MI, Giardini V, Cardellicchio M, Calabrese S, Algeri P, et al. PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction. J Matern Fetal Neonatal Med 2017;30:144-9.
Bruno S, Deregibus MC, Camussi G. The secretome of mesenchymal stromal cells: Role of extracellular vesicles in immunomodulation. Immunol Lett 2015;168:154-8.
Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis 2016;7:e2062.
Legaki E, Roubelakis MG, Theodoropoulos GE, Lazaris A, Kollia A, Karamanolis G, et al. Therapeutic potential of secreted molecules derived from human amniotic fluid mesenchymal stem/Stroma cells in a mice model of colitis. Stem Cell Rev Rep 2016;12:604-12.
Teixeira FG, Panchalingam KM, Anjo SI, Manadas B, Pereira R, Sousa N, et al. Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of wharton jelly mesenchymal stem cell secretome? Stem Cell Res Ther 2015;6:133.
Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: Pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol 2019;15:275-89.
Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. J Hum Hypertens 2017;31:782-6.
Fisher SJ. Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol 2015;213:S115-22.
Lu L, Kingdom J, Burton GJ, Cindrova-Davies T. Placental stem villus arterial remodeling associated with reduced hydrogen sulfide synthesis contributes to human fetal growth restriction. Am J Pathol 2017;187:908-20.
Boomsma RA, Geenen DL. Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis. PLoS One 2012;7:e35685.
Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R, et al. The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration. Cytotherapy 2016;18:13-24
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
