Dr Ursula Manuelpillai - Researcher Profile

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Address

Monash Institute of Medical Research
Centre for Reproduction & Development

Contact Details

Tel: +61 3 990 24803

Email: Ursula.Manuelpillai@monash.edu


Biography

Power of placenta could treat killer diseases

Around 450 million people worldwide suffer from liver fibrosis, a debilitating condition that can lead to cirrhosis and liver failure. But hope for a new treatment is emerging from Dr Ursula Manuelpillai’s research into the healing capabilities of cells from the placenta. She says the remarkable capacity of these powerful cells could lead to treatments for a range of chronic inflammatory and possibly autoimmune diseases.

Liver fibrosis is a condition caused by alcohol abuse or diseases such as hepatitis, in which scar tissue replaces healthy liver cells. Cirrhosis is an extreme form of the condition and a precursor to liver cancer and liver failure.

In a remarkable breakthrough, Ursula and a collaborator have found that placental cells could be used to repair damaged tissue and reduce inflammation.

The body’s immune system ordinarily rejects any foreign tissue or pathogens. This is one of the reasons why organ transplants sometimes fail. The body rejects or attacks the transplanted organ. However, Ursula says placental cells have special properties that make them less likely to be rejected if implanted to help repair damaged tissue.

Cells in the placenta have the same DNA as the baby, rather than the mother. However, the woman’s body tolerates these genetically different cells. “Placental cells can suppress the mother’s immune system and possess clever ways to avoid detection. This means you could potentially transplant these cells into other adults,” Ursula says.

Based at the Monash Institute of Medical Research, which shares a site with the Monash Medical Centre (MMC), she focuses specifically on the cells that make up the sack within the uterus where the baby floats in amniotic fluid. These cells are known as human amniotic epithelial cells, or hAECs.


Her main collaborator is Professor William Sievert from Monash University’s Department of Medicine at the MMC. Their project is funded by a National Health and Medical Research Council grant of more than $600,000.

Their research has found when animals with a disorder mimicking human liver cirrhosis are injected with placental cells the amount of liver damage declines. The treatment could slow or even reverse liver cirrhosis in patients suffering chronic liver disease, potentially making liver transplants unnecessary for them.

At the moment the best treatment for cirrhosis is a liver transplant. But as organ donation rates in the Western world fall, finding compatible organs for transplant becomes more difficult.

The next step is to work out why the cells have the effect that they do, by examining what happens at a molecular level. Ursula and William also hope to secure funding that will enable them to use hAECs to grow liver cells for transplantation.

Ursula is a regular speaker at schools and at organisations such as Probus and Rotary and is passionate about sharing science with the community.

“Many people are keen to learn more and are excited about my work, particularly those who know someone who is having a baby. They often want to know whether it is possible to hold onto the placenta for potential future use or how they could assist our work.”

She says her research could also shed light on some lung diseases, including asthma, emphysema and conditions caused by excessive smoke inhalation. These diseases involve mechanisms similar to cirrhosis. Respiratory diseases affect more than 500 million people worldwide.

Keywords

placental stem cells, pre-clinical animal disease models, stem cell biology, transdifferentiation of stem cells, xenotransplantation and immunological properties of stem cells

Qualifications

PHD
Institution: Victoria University of Technology
Year awarded: 2000
POSTGRADUATE DIPLOMA IN BIOTECHNOLOGY
Institution: University of Melbourne
Year awarded: 1994
Unknown
Institution: University of Coldmbo
Year awarded: 1981

Publications

Journal Articles

Liu, Y., Vaghjiani, V., Tee, J.Y., To, K.Y., Cui, P., Oh, D.Y., Manuelpillai, U.C., Toh, B., Chan, J.W., 2012, Amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis, PLoS ONE [P], vol 7, issue 4, Public Library of Science, United States, p. e35758.

Liu, Y., Vaghjiani, V., Tee, J., To, K., Cui, P., Oh, D., Manuelpillai, U., Toh, B., Chan, M., 2012, Amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis, PLoS ONE [P], vol 7, issue 4 (e35758), Public Library of Science, United States, pp. 1-9.

Heffernan, C., Sumer, H., Guillemin, G.J., Manuelpillai, U.C., Verma, P.J., 2012, Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis, PLoS ONE [P], vol 7, issue 9 (Art. ID: e45501), Public Library of Science, United States, pp. 1-12.

Manuelpillai, U.C., Lourensz, D., Vaghjiani, V., Tchongue, J., Lacey, D., Tee, J.Y., Murthi, P., Chan, M.K.J., Hodge, A., Sievert, W., 2012, Human amniotic epithelial cell transplantation induces markers of alternative macrophage activation and reduces established hepatic fibrosis, PLoS ONE [P], vol 7, issue 6 (Art. No: e38631), Public Library of Science, United States, pp. 1-11.

Manuelpillai, U., Moodley, Y., Borlongan, C., Parolini, O., 2011, Amniotic membrane and amniotic cells: Potential therapeutic tools to combat tissue inflammation and fibrosis?, Placenta [P], vol 32, issue Supp 4, Elsevier Ltd, United Kingdom, pp. S320-S325.

Moodley, Y., Manuelpillai, U., Weiss, D., 2011, Cellular therapies for lung disease: A distant horizon, Respirology [P], vol 16, issue 2, Wiley-Blackwell Publishing Asia, Australia, Japan, pp. 223-237.

Pratama, G., Vaghjiani, V., Tee, J., Liu, Y., Chan, M., Tan, C., Murthi, P., Gargett, C., Manuelpillai, U., 2011, Changes in culture expanded human amniotic epithelial cells: Implications for potential therapeutic applications, PLoS ONE [P], vol 6, issue 11 (Art. No: e26136), Public Library of Science, United States, pp. 1-12.

Li, Y., Puryer, M., Lin, E., Hale, K., Salamonsen, L., Manuelpillai, U., Tong, S., Chan, W., Wallace, E., Nie, G., 2011, Placental HtrA3 is regulated by oxygen tension and serum levels are altered during early pregnancy in women destined to develop preeclampsia, Journal of Clinical Endocrinology and Metabolism [P], vol 96, issue 2, The Endocrine Society, United States, pp. 403-411.

Novakovic, B., Gordon, L., Wong, N., Moffett, A., Manuelpillai, U., Craig, J., Sharkey, A., Saffery, R., 2011, Wide-ranging DNA methylation differences of primary trophoblast cell populations and derived cell lines: Implications and opportunities for understanding trophoblast function, Molecular Human Reproduction [P], vol 17, issue 6, Oxford University Press, United Kingdom, Belgium, pp. 344-353.

Novakovic, B., Wong, N., Sibson, M., Ng, H., Morley, R., Manuelpillai, U., Down, T., Rakyan, V., Beck, S., Hiendleder, S., Roberts, C., Craig, J., Saffery, R., 2010, DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta, Journal Of Biological Chemistry [P], vol 285, issue 13, American Society for Biochemistry and Molecular Biology, Inc., United States, pp. 9583-9593.

Chui, A., Pathirage, N., Johnson, B., Cocquebert, M., Fournier, T., Evain-Brion, D., Roald, B., Manuelpillai, U., Brennecke, S., Kalionis, B., Murthi, P., 2010, Homeobox gene distal-less 3 is expressed in proliferating and differentiating cells of the human placenta, Placenta [P], vol 31, issue 8, Elsevier Ltd, United Kingdom, pp. 691-697.

Moodley, Y., Ilancheran, S., Samuel, C., Vaghjiani, V., Atienza, D., Williams, E., Jenkin, G., Wallace, E.M., Trounson, A.O., Manuelpillai, U.C., 2010, Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair, American Journal Of Respiratory And Critical Care Medicine [P], vol 182, issue 5, American Thoracic Society, USA, pp. 643-651.

Ligam, P., Manuelpillai, U., Wallace, E., Walker, D., 2010, NFkappaB-dependent increase of kynurenine pathway activity in human placenta: Inhibition by sulfasalazine, Placenta [P], vol 31, issue 11, Elsevier Ltd, United Kingdom, pp. 997-1002.

Manuelpillai, U., Tchongue, J., Dowling, D., Vaghjiani, V., Samuel, C., Liu, A., Williams, E., Sievert, W., 2010, Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl 4-treated mice, Cell Transplantation [P], vol 19, issue 9, Cognizant Communication Corp., United States, pp. 1157-1168.

Ilancheran, S., Moodley, Y., Manuelpillai, U.C., 2009, Human Fetal Membranes: A Source of Stem Cells for Tissue Regeneration and Repair?, Placenta [P], vol 30, issue 1, Elsevier, UK, pp. 2-10.

Moodley, Y., Atienza, D., Manuelpillai, U.C., Samuel, C.S., Tchongue, J., Ilancheran, S., Boyd, R.L., Trounson, A.O., 2009, Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury, American Journal Of Pathology [P], vol 175, issue 1, American Society for Investigative Pathology, USA, pp. 303-313.

Paiva, P., Salamonsen, L.A., Manuelpillai, U.C., Dimitriadis, E., 2009, Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation, Biology of Reproduction, vol 80, Society for the Study of Reproduction, Madison WI USA, pp. 302-310.

Novakovic, B., Sibson, M., Ng, H.K., Manuelpillai, U.C., Rakyan, V., Down, T., Beck, S., Fournier, T., Evain-Brion, D., Dimitriadis, E., Craig, J.M., Morley, R., Saffery, R., 2009, Placenta-specific methylation of the vitamin D 24-hydroxylase gene. Implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface, Journal Of Biological Chemistry [P], vol 284, issue 22, American Society for Biochemistry and Molecular Biology, Inc, United States, pp. 14838-14848.

Dias, V.L., Meachem, S.J., Rajpert-De Meyts, E., McLachlan, R., Manuelpillai, U.C., Loveland, K.A.L., 2008, Activin receptor subunits in normal and dysfunctional adult human testis, Human Reproduction, vol 23, Oxford University Press, England, pp. 412-420.

Tapia, A., Salamonsen, L.A., Manuelpillai, U.C., Dimitriadis, E., 2008, Leukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of tissue inhibitor of metalloproteinases-1 and -2, Human Reproduction, vol 23, issue 8, Oxford University Press, UK, pp. 1724-1732.

Novakovic, B., Rakyan, V., Ng, H.K., Manuelpillai, U.C., Dewi, C., Wong, N.C., Morley, R., Down, T., Beck, S., Craig, J.M., Saffery, R., 2008, Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts, Molecular Human Reproduction, vol 14, issue 9, Oxford University Press, UK, pp. 547-554.

Paiva, P., Salamonsen, L.A., Manuelpillai, U.C., Walker, C., Tapia, A., Wallace, E.M., Dimitriadis, E., 2007, Interleukin-11 promotes migration, but not proliferation, of human trophoblast cells, implying a role in placentation, Endocrinology, vol 148, issue 11, The Endocrine Society, USA, pp. 5566-5572.

Mandang, S., Manuelpillai, U.C., Wallace, E.M., 2007, Oxidative stress increases placental and endothelial cell activin A secretion, Journal of Endocrinology, vol 192, issue 3, Society for Endocrinology, UK, pp. 485-493.

Ilancheran, S., Michalska, A.E., Peh, G.S.L., Wallace, E.M., Pera, M.F., Manuelpillai, U.C., 2007, Stem Cells Derived from Human Fetal Membranes Display Multilineage Differentiation Potential, Biology of Reproduction, vol 77, issue 3, Society for the Study of Reproduction, USA, pp. 577-588.

Nie, G., Hale, K., Li, Y., Manuelpillai, U.C., Wallace, E.M., Salamonsen, L.A., 2006, Distinct expression and localization of serine protease HtrA1 in human endometrium and first-trimester placenta, Developmental Dynamics, vol 235, issue 12, Wiley-Liss, Hoboken USA, pp. 3448-3455.

Hardman, B., Manuelpillai, U.C., Wallace, E.M., Monty, J., Kramer, D.R., Kuo, Y.M., Mercer, J.F.B., Ackland, M.L., 2006, Expression, localisation and hormone regulation of the human copper transporter hCTR1 in placenta and choriocarcinoma Jeg-3 cells, Placenta, vol 27, issue 9-10, W B Saunders Co. Ltd, UK, pp. 968-977.

Nie, G., Li, Y., Hale, K., Okada, H., Manuelpillai, U.C., Wallace, E.M., Salamonsen, L.A., 2006, Serine peptidase HTRA3 is closely associated with human placental development and is elevated in pregnancy serum, Biology of Reproduction, vol 74, issue 2, The Society for the Study of Reproduction, Inc., Madison USA, pp. 366-374.

Manuelpillai, U.C., Ligam, P., Smythe, G., Wallace, E.M., Hirst, J.J., Walker, D.W., 2005, Identification of kynurenine pathway enzyme mRNAs and metabolites in human placenta: up-regulation by inflammatory stimuli and with clinical infection, American Journal of Obstetrics & Gynaecology, vol 192, issue 1, Mosby, Inc., USA, pp. 280-288.

Ligam, P., Manuelpillai, U.C., Wallace, E.M., Walker, D.W., 2005, Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: implications for role of the kynurenine pathway in pregnancy, Placenta, vol 26, issue 6, W B Saunders Co. Ltd, UK, pp. 498-504.

Hardman, B., Manuelpillai, U.C., Wallace, E.M., Van de Waasenburg, S., Cater, M., Mercer, J.F.B., Ackland, M.L., 2004, Expression and localization of Menkes and Wilson copper transporting ATPases in human placenta, Placenta, vol 25, issue 6, W B Saunders Co Ltd, London England, pp. 512-517.

Madsen, G., Zakar, T., Manuelpillai, U.C., Wallace, E.M., Kwek, K., Yeoh, G.S.H., Smith, R.K., Mesiano, S., 2004, Intracrine control of estrogen action in human gestational tissues at parturition, Journal of the Society for Gynecologic Investigation, vol 11, issue 4, Elsevier, New York USA, pp. 213-219.

Tong, S., Marjono, A.B., Brown, D.A., Mulvey, S.F., Breit, S.N., Manuelpillai, U.C., Wallace, E.M., 2004, Serum Concentrations of Macrophage Inhibitory Cytokine 1 (MIC 1) as a predictor of miscarriage, Lancet, vol 363, issue 9403, Lancet Ltd, London England, pp. 129-130.

Tong, S., Marjono, A.B., Brown, D.A., Mulvey, S.F., Breit, S.N., Manuelpillai, U.C., Wallace, E.M., 2004, Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor of miscarriage, The Lancet, vol 363, issue 9403, Lancet Ltd, London England, pp. 129-130.

Manuelpillai, U.C., Schneider-Kolsky, M.E., Thirunavukarasu, P.P., Dole, A., Waldron, K., Wallace, E.M., 2003, Effect of hypoxia on placental activin A, inhibin A and follistatin synthesis, Placenta, vol 24, issue 1, Elsevier Science Ltd, London UK, pp. 77-83.

Weston, G.C., Trajstman, A.C., Gargett, C.E., Manuelpillai, U.C., Vollenhoven, B.J., Rogers, P.A.W., 2003, Fibroids display an anti-angiogenic gene expression profile when compared with adjacent myometrium, Molecular Human Reproduction, vol 9, issue 9, Oxford University Press, Oxford England, pp. 541-549.

Manuelpillai, U.C., Nicholls, T.A., Wallace, E.M., Phillips, D.J., Guillemin, G., Walker, D.W., 2003, Increased mRNA expression of kynurenine pathway enzymes in human placentae exposed to bacterial endotoxin, Advances in Experimental Medicine and Biology, vol 527, Kluwer Academic/Plenum Publishers, USA, pp. 85-89.

Marjono, A.B., Brown, D.A., Horton, K.E., Wallace, E.M., Breit, S.N., Manuelpillai, U.C., 2003, Macrophage inhibitory cytokine-1 in gestational tissues and maternal serum in normal and pre-eclamptic pregnancy, Placenta, vol 24, issue 1, WB Saunders Co Ltd, Elsevier Science Ltd, London UK, pp. 100-106.

Santoso, D., Rogers, P., Wallace, E.M., Manuelpillai, U.C., Walker, D.W., Bekti Subakir, S., 2002, Localization of Indoleamine 2,3-Dioxygenase and 4-Hydroxynonenal in Normal and Pre-eclamptic Placentae, Placenta, vol 23, issue 5, WB Saunders, Elsevier Science Ltd, London UK, pp. 373-379.

Schneider-Kolsky, M.E., Manuelpillai, U.C., Waldron, K., Dole, A., Wallace, E.M., 2002, The Distribution of Activin and Activin Receptors in Gestational Tissues Across Human Pregnancy and During Labour, Placenta, vol 23, issue 4, WB Saunders Co Ltd, London UK, pp. 294-302.

Manuelpillai, U.C., Schneider-Kolsky, M.E., Dole, A., Wallace, E.M., 2001, Activin A and activin receptors in gestational tissue from preeclamptic preganacies, Journal of Endocrinology, vol 171, issue 1, Society for Endocrinology, Stookebristol UK, pp. 57-64.

Schneider-Kolsky, M.E., Manuelpillai, U.C., Gargett, C., Wallace, E.M., 2001, Activin bA-subunit and activin receptors in human myometrium at term and during labour, British Journal of Obstetrics and Gynaecology, vol 108, issue 8, Elsevier Science BV, Amsterdam Netherlands, pp. 869-874.

Conference Proceedings

Manuelpillai, U.C., Ligam, P., Walker, D.W., Wallace, E.M., 2006, Effects of betamethasone and sulfasalazine on placental production of the neurotoxin quinolinic acid, Journal of The Society for Gynecologic Investigation, 22-25 March, Elsevier Science Inc, New York NY USA, p. 182A.

Other

Parolini, O., Alviano, F., Betz, A., Bianchi, D., Gotherstrom, C., Manuelpillai, U., Mellor, A., Ofir, R., Ponsaerts, P., Scherjon, S., Weiss, M., Wolbank, S., Wood, K., Borlongan, C., 2011, Meeting report of the first conference of the International Placenta Stem Cell Society (IPLASS), Meeting report of the first conference of the International Placenta Stem Cell Society (IPLASS), Elsevier Ltd, United Kingdom.

Lash, G., Burton, G., Chamley, L., Clifton, V., Constancia, M., Crocker, I., Dantzer, V., Desoye, G., Drewlo, S., Hemmings, D., Hiendleder, S., Kalionis, B., Kellan, J., Kudo, Y., Lewis, R., Manuelpillai, U., Murthi, P., Natale, D., Pfarrer, C., Robertson, S., Saffery, R., Saito, S., Sferruzzi-Perri, A., Sobrevia, L., Waddell, B., Roberts, C., 2010, IFPA Meeting 2009 workshops report, This report is a full summary of the varoius topics covered at the Annual Meeting of the International Federation of Placenta Associations (IFPA), Elsevier Ltd., United Kingdom.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Differentiation and encapsulation of hepatocyte-like cells derived from human amniotic epithelial cells.
Supervisors:
Manuelpillai, U (Joint-co), St John, J (Joint).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Mechanisms of fibrosis resolution in human amniotic epithelial cell therapy for liver fibrosis .
Supervisors:
Manuelpillai, U (Joint), Sievert, W (Joint-co).

Completed Supervision

Student:
Ilancheran, S.
Program of Study:
Stem cell properties of human amniotic epithelial cells. (PHD) 2007.
Supervisors:
Manuelpillai, U (Main), Wallace, E (Associate).
Student:
Lin, S.
Program of Study:
. 2008.
Supervisors:
Manuelpillai, U (Main).
Student:
Marjono, A.
Program of Study:
Macrophage inhibitory cytokine-1 at the maternal-placental interface of early human pregnancy. (PHD) 2005.
Supervisors:
Wallace, E (Main), Manuelpillai, U (Associate).
Student:
Pratama, G.
Program of Study:
CHARACTERISATION OF PRIMARY AND EXPANDED HUMAN AMNION EPITHELIAL CELLS FOR POTENTIAL CELLULAR THERAPEUTIC APPLICATIONS. (Masters) 2010.
Supervisors:
Manuelpillai, U (Main).
Student:
Walker, C.
Program of Study:
Endogenous opioids at the maternal-placental interface during early pregnancy. (Masters) 2007.
Supervisors:
Manuelpillai, U (Main), Wallace, E (Associate).