Bill Kalionis

Bill Kalionis, B.Sc (Hons), PhD

Head of the Stem Cell Laboratory and a Senior Research Fellow in the Department of Maternal-Fetal Medicine Pregnancy Research Centre

Bill is a molecular biologist with a background in Biochemistry and Genetics. He has supervised numerous PhD and honours students.

Bill has been invited to speak at national and international meetings including the International Federation of Placenta Associations (IFPA) Meetings and ANZPRA.

He has received peer-reviewed research grants from the NHMRC, ARC, Clive and Vera Ramaciotti and Kathleen Cuningham Foundations. Since 2005, Bill has led the Stem Cell Laboratory and has focussed on an important stem cell type in the human placenta; the mesenchymal stem cell.


 

Stem Cell Laboratory

Mesenchymal stem cells are "mother cells" that have the potential to form cells of the placenta. This allows the placenta to grow, and in doing so, nurture the rapidly growing fetus.

Placental mesenchymal stem cells are remarkable cells. Not only can they form the cells of the placenta but if treated with special combinations of growth factors they can also be triggered to form bone, fat, cartilage and muscle cells. Other laboratories have coaxed placental mesenchymal stem cells to form cells that are similar to liver cells and even nerve cells.

These special properties of placental mesenchymal stem cells make them suitable for many clinical studies that assess their ability to renew or repair a wide range of diseased or damaged tissues. These studies require 10-100 million cells to treat each patient. The average placenta (~0.7kg) is an abundant source of mesenchymal cells, with the additional important advantage that the mesenchymal stem cells can be obtained through non-invasive means with minimal ethical concerns. Placentas represent an immense, underutilized resource for the harvesting and production of large quantities of mesenchymal stem cells.

Cell and tissue damage are a feature of the clinically important pregnancy disorders of preeclampsia and fetal growth restriction. The long term research goal of the Kalionis laboratory is to exploit the regenerative and repair capacity of mesenchymal stem cells to develop new therapies to reduce or repair the cell and tissue damage associated with preeclampsia and fetal growth restriction.

Current Stem Cell projects

Using placental tissue to improve stem cell growth. CI's: Heath, Kalionis, Manuelpillai, Brennecke, Simpson (#14-35 2014-2016) 

Adult stem cells isolated from various tissues have attracted great clinical interest for their therapeutic potential. A major bottleneck in the clinical use of adult stem cells is the need to greatly expand their numbers in cell culture to achieve clinically useful numbers of cells. However, cell culture expansion of adult stem cells results in the loss of important properties. Growing adult stem cells on biological surfaces that are prepared from immature stem cells shows promise in improving growth and maintaining adult stem cell properties during cell culture expansion. However, fetus-derived immature stem cells have significant legal and ethical concerns as sources for the preparation of biological substrates. The placenta, umbilical cord and fetal membranes are abundant, readily available and ethically acceptable sources of immature stem cells, which can be used to prepare biological surfaces. The general hypothesis is that biological substrates derived from stem cells of the placenta, umbilical cord and fetal membranes are a superior platform for the growth and maintenance of adult stem cells.

Isolation and characterisation of mesenchymal stem cells obtained from chorionic villous sampling. CI's Kalionis, Pertile (#30154A 2011-2016)

We have shown the term placenta (~39 weeks) is a rich source of stem cells but we do not know if the properties of these stem cells change with gestational age. Recently, it has been discovered that stem cells can be obtained from placental cells which have been cultured in the laboratory for the purpose of chorionic villus sampling (CVS). CVS is a highly accurate antenatal test for chromosome abnormalities, which is usually performed in the first trimester of pregnancy (11-12 weeks).  After analysis, the cells are routinely discarded, but stem cells can be obtained from these cultured cells. In this project, we will carry out a comprehensive comparison of the gene expression and functional properties of first trimester stem cells. These properties of stem cells obtained from first trimester CVS cultured cells will be compared to term placental stem cells.

Isolation and Characterisation of breast milk stem cells Kalionis. CI's Theda, Brennecke, Jacobs, Amir (#13/42 2014-2016) 

This is a pilot project with the general aim of isolating and characterising stem cells from breast milk. We will also compare their properties with those of placental stem cells. We will use published methods to isolate breast milk stem cells, determine the yield of stem cells and the type of stem cells that have been isolated. The breast milk stem cell properties will be analysed by a variety of assays to determine whether the cells that were isolated have stem cell properties. We have published the methodologies we will use to characterise the breast milk stem cells and will compare the properties found to those of placental stem cells. These methods include the ability of the stem cells to divide and the expression of characteristic stem cell associated proteins found on the cell surface. We will also stimulate the stem cells in culture with various combinations of growth factors and determine whether they are able to form different cell types such as bone, fat, cartilage and muscle cells. Finally, we will use published methods to determine which genes and proteins are expressed in breast milk stem cells and which proteins and other factors are secreted by breast milk stem cells. At the conclusion of the pilot study, we will have completed our characterisation of the breast milk stem cells and to have compared them to placental stem cells. This information will allow us to determine the utility of breast milk stem cells for future studies, which will investigate the production, composition and characteristics of breast milk stem cells at various stages of lactation. Future studies will include characterisation of breast milk stem cells in women who are breastfeeding infants that face specific nutritional or health challenges such as infants with intrauterine growth restriction or infants born preterm.

Reduced stem cell resistance to oxidative stress contributes to the pathogenesis of preeclampsia. CI's Kalionis Brennecke (#12/42 2012-2015)      

Damage to blood vessel walls is thought to be a key step in the causation of preeclampsia. This damage is caused by stress factors in the blood, which are at much higher levels in preeclampsia affected blood vessels than blood vessels in normal pregnancy. We need to understand how cells respond to high levels of stress in order to design new therapies to combat cell stress and minimise blood vessel wall damage. We showed that stem cells are intimately associated with blood vessel walls in the decidua, the tissue located between the placenta and the muscular uterine wall, which plays a crucial role in pregnancy. Decidua is a major source of stress products in preeclampsia and stem cells in the blood vessel walls are exposed to these stress products that cause damage to blood vessel walls. We have evidence that stem cells have reduced capacity to respond to cell stress in preeclampsia. The overall hypothesis of the project is that the reduced ability of decidua stem cells to respond to stress contributes to the development of preeclampsia. The overall aim is to identify important stress genes that are abnormal in preeclampsia affected decidua stem cells.

Abnormal stem cells and their role in the most common, serious human pregnancy disorder: Pre-Eclampsia. CI's Kalionis, Murthi, Gude, Brennecke (#10/49 2011-2014)     

The therapeutic potential of human placental mesenchymal stem cells drives current research. But, the function of these stem cells in the placenta and their contribution to human pregnancy disorders is unknown. In many organs, mesenchymal stem cells are found between endothelial cells of the vessel walls and the surrounding smooth muscle cells, and they interact with these two cell types and modify their functions. We have shown this same arrangement of cells in the maternal decidual blood vessels. These vessels are critical to early placental development as they are invaded by specialised fetal trophoblast cells, which replace the smooth muscle cells and endothelial cells. This creates modified maternal vessels capable of supplying sufficient blood to the placenta, which is essential to support the rapidly growing fetus. We propose that decidua basalis mesenchymal stem cells (DMSCs) play an important role in the remodelling of maternal uterine vessels. This is a novel concept in placental biology. 
Pre-eclampsia (PE) is a disorder characterised by the pregnancy-induced onset of hypertension, proteinuria, and edema in the mother. PE is the most common and serious disorder of human pregnancy. Severe PE affects about 1-2% of all pregnancies (5,000 cases per annum) in Australia whilst mild PE affects up to 10% of all pregnancies.  One of the hallmarks of PE is shallow invasion of the maternal uterine vessels. In PE, we have evidence that DMSCs are abnormal and predict there are adverse consequences on the functions of smooth muscle cells and endothelial cells. This project will establish DMSCs as a new and potentially important player in the pathobiology of pre-eclampsia. In this study, our overall aims are to;

  1. Investigate the function(s) of DMSCs in normal placental development and in pre-eclampsia.
  2. Explore the molecular mechanisms underlying defective DMSC functions by identifying genes and biological pathways that show altered expression in PE-affected DBMSCs.

Identification, isolation, characterisation and culturing of stem cells from the placenta and umbilical cord. CI's Kalionis, Murthi, Gude, Brennecke (#05/07 2005-2010)     

The project has two main aims. Firstly, we will identify, isolate, characterise and culture stem cells from the placenta and umbilical cord. We will show they are stem cells by influencing them to form certain cell types (bone, cartilage and fat cells) upon addition of growth factors. Secondly, we will establish a novel assay to allow us to study stem cells in placental tissues. By adding growth factors and other molecules that are known to result in increased stem cell movement, we will be able to study how placental stem cells move into and out of placental vessels. These studies will provide a better understanding of the properties of stem cells in the human placenta. Furthermore, following thorough characteristion, the stem cells may in future be used for novel therapies to treat repair and treat organ damage.

Stem Cell Team

Senior Staff:
Dr Bill Kalionis, Dr Harry Georgiou, Dr Padma Murthi, Dr Maria Kokkinos, Dr Ursula Manuelpillai, Prof Shaun Brennecke

PhD Students:
Gina Kusuma, Batla Al Sowayan, Aida Shakouri, Sharon Qin

Honours Students:
Clare Vincent, Sarah Wilkinson

Masters Student:
Jancy Johnson

Research Assistants:
Anthony Borg, Janet Stevenson

Research Midwives:
Sue Duggan, Moira Stewart

Visiting Researchers:
Haiying Lui, Aiwu Shi

Collaborators:
Dr Daniel Heath, Department of Chemical and Biomolecular Engineering, University of Melbourne, Victoria, Australia
Dr Christiane Theda, Newborn Research Centre, Royal Women’s Hospital, Victoria , Australia
Dr Mark Pertile, VCGS, Murdoch Children’s Research Institute, Royal Children's Hospital, Victoria, Australia
Dr Ursula Manuelpillai, Department of Perinatal Medicine Pregnancy Research Centre,Royal Women's Hospital; Centre for Genetic Diseases, Monash Institute of Medical Research, Monash University; Prince Henry's Institute of Medical Research, Monash University, Victoria , Australia
Prof Stan Gronthos, Mesenchymal Stem Cell Laboratory, Faculty of Health Sciences, School of Medical Sciences, University of Adelaide; Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, Australia
Prof Andrew Zannettino, South Australian Health and Medical Research Institute, Adelaide, Australia
Dr Mohamed Abumaree, King Saud Bin Abdulaziz University for Health Sciences/King Abdullah International Medical Research Center, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
Dr Shijin Xia, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, China 
Prof Yoel Sadovsky, Magee Womens Research Institute, University of Pittsburgh, Pittsburgh, USA
Prof Aiko Okamoto, Department of Obstetrics and Gynecology,The Jikei University School of Medicine, Tokyo, Japan
Prof Martin Knoefler, Medical University of Vienna, Vienna, Austria

Past Staff:
Melissa Duggan, Dr Rishka Pace, Deborah Singhh

Past Students:
Dr Natalie Castrechini, Christopher Turner, Rosemary Gunawan, Wei-I-Lee, Anastasia Agusto, Sophia Hill, Pamela Anjara, Deborah Singhh

Student Awards and Prizes

Gina Kusma
Australian Stem Cell Centre Scholarship from Australian Stem Cell Centre (ASCC)
APA Scholarship from the University of Melbourne
The Elsevier Placenta New Investigator Award 2013 for the best oral presentation by a new investigator at the International Federation of Placenta Associations (IFPA), Whistler, Canada, September 2013
Y.W. Loke Award, Travel Award, International Federation of Placenta Associations (IFPA) 2013, Whistler, Canada, September 2013
Student Travel Fellowship from Singapore Stem Cell Society (SSCS) to attend SCSS Symposium, Singapore, 2012
Student Travel Award from Australasian Society for Stem Cell Research (ASSCR) to attend AHRMC Congress, Adelaide, 2012
Student Travel Grant from Society of Reproductive Biology to attend World Congress of Reproductive Biology, Cairns, 2011

Batla Al Sowayan
National Guard Scholarship, Saudi Arabia
Student Travel Grant from Society of Reproductive Biology to attend World Congress of Reproductive Biology in Cairns, 2011

Sharon Qin
University of Melbourne Felix Meyer Scholarship
Recipient of a Royal Women’s Hospital Scholarship

Christopher Turner
Department of Obstetrics and Gynaecology, Honours Award, Royal Melbourne Hospital Academic Centre

Dr Natalie Castrechini
Recipient of a Wenkart scholarship (extended)
Recipient of a University of Melbourne Department of Obstetrics and Gynaecology Departmental Scholarship
Recipient of a Royal Women’s Hospital Travel Grant
Recipient of a Loke New Investigator Travel Award, 13th International Federation for Placental Associations Conference, Kingston Canada,17-25 August 2007
Received a poster of merit award, 13th International Federation for Placental Associations Conference, Kingston Canada,17-25 August 2007
Recipient of a ISSCR Travel Award to attend the ISSCR International Conference, Cairns, Queensland 17-20 June 2007

Stem Cell publications

Kusuma G, Murthi P, Kalionis B. Function and Pathologies of the Human Placenta “Placenta: The Tree of Life” Parolini O ed. In Press

Kusuma GD, Manuelpillai U, Abumaree M, Pertile MD,  Brennecke SP, Kalionis B. (2015) Mesenchymal stem cells reside in a vascular niche in the decidua basalis, and are absent in remodelled spiral arterioles Placenta.  36 312-321.

Abomaray FM, Al Jumah MA, Kalionis B, Al Askar AS, Al Harthy, Jawdat SD, Al Khaldi A  BA. Knawy , Abumaree MH. Human chorionic villous mesenchymal stem cells modify the functions of human dendritic cells, and induce an anti-inflammatory phenotype in CD1+ dendritic cells. Stem Cell Reviews and Reports. Oct 7. [Epub ahead of print]

Abumaree MH, Al Askar AS, Kalionis B, Hajeer AH, Fakhoury H, Al Jumah MA. (2014) Stem cell research and regenerative medicine at King Abdullah International Medical Research Center (KAIMRC). Stem Cells and Development. 23 Suppl 1:12-6.

Liu H, Murthi P, Qin S, Kusuma GD, Borg A, Knöfler M, Haslinger P, Manuelpillai U , Pertile MD, Abumaree M, Kalionis B (2014). A novel combination of homeobox genes is expressed in mesenchymal chorionic stem/stromal cells in first trimester and term pregnancies. Reproductive Sciences. 21(11):1382-94.

Ning Y, Huang J, Kalionis B, Bian Q, Dong J, Wu J, Wu J, Xia S. Oleanolic acid induces differentiation of neural stem cells to neurons: an involvement of transcription factor Nkx-2.5. BioMed Research International, Stem Cells International Special issue: "Application of Adult Stem Cells in Medicine” Received 29 September 2014; Accepted 16 January 2015 Article ID 672312

Vaghjiani V, Vaithilingam V, Saraswati I, Sali A, Murthi P, Kalionis B, Tuch BE, Manuelpillai U. (2014) Hepatocyte-like cells derived from human amniotic epithelial cells can be encapsulated without loss of viability or function in vitro. Stem Cells and Development. 15;23(8):866-76

Wan W-b, Cao L, Kalionis B , Xia  S. Applications of induced pluripotent stem cells in studying the neurodegenerative diseases. BioMed Research International, Stem Cells International Special issue: "Application of Adult Stem Cells in Medicine" Accepted 09 Dec 2014 Article ID 382530

Abumaree MH, Al Jumah MA, Kalionis B, Jawdat D, Al Khaldi A, Abomaray FM, Fatani AS, Chamley LW, Knawy BA. (2013) Human placental mesenchymal stem cells (pMSCs) play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1 to anti-inflammatory M2 macrophages. Stem Cell Reviews and Reports. 9(5):620-641

Abumaree MH, Al Jumah MA, Kalionis B, Jawdat D, Al Khaldi A, Al Talabani AA, Knawy BA. (2013) Phenotypic and functional characterization of mesenchymal stem cells from chorionic villi of human term placenta. Stem Cell Reviews and Reports. 9(1):16-31

Castrechini NM, Murthi P, Qin S, Kusuma GD, Wilton L, Abumaree M, Gronthos S, Zannettino A, Gude NM, Brennecke SP, Kalionis B. (2012) Decidua Parietalis-derived Mesenchymal Stromal Cells reside in a Vascular Niche within the Choriodecidua Reproductive Sciences 19(12):1302-14

Ackerman WE 4th, Bulmer JN, Carter AM, Chaillet JR, Chamley L, Chen CP, Chuong EB, Coleman SJ, Collet GP, Croy BA, de Mestre AM, Dickinson H, Ducray J, Enders AC, Fogarty NM, Gauster M, Golos T, Haider S, Heazell AE, Holland OJ, Huppertz B, Husebekk A, John RM, Johnsen GM, Jones CJ, Kalionis B, König J, Lorenzon AR, Moffett A, Moreira de Mello JC, Nuzzo AM, Parham P, Parolini O, Petroff MG, Pidoux G, Ramírez-Pinilla MP, Robinson WP, Rolfo A, Sadovsky Y, Soma H, Southcombe JH, Tilburgs T, Lash GE. (2012) IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells. Placenta. 33 Suppl:S15-22.

Abumaree M, Al Jumah M, Pace RA, Kalionis B. (2012) Immunosuppressive properties of mesenchymal stem cells. Stem Cell Reviews and Reports. 8:375-392 

Betts D, Kalionis B, Hillier S. (2010) Stem cells roles in reproduction: what is the basic science? (Editorial) Molecular Human Reproduction. 16(11):791-2

Lash GE, Burton GJ, Chamley LW, Clifton VL, Constancia M, Crocker IP, Dantzer V, Desoye G, Drewlo S, Hemmings DG, Hiendleder S, Kalionis B, Keelan JA, Kudo Y, Lewis RM, Manuelpillai U, Murth P, Natale D, Pfarrer C, Robertson S, Saffery R, Saito S, Sferruzzi-Perri A, Sobrevia L, Waddell BJ, Roberts CT. (2010) IFPA Meeting 2009 workshops report Placenta. Suppl. 31, S4-20 

Castrechini NM, Murthi P, Gude NM, Erwich JJH, Gronthos S, Zannettino A, Brennecke SP, Kalionis B. (2010) Mesenchymal stem cells in human placental chorionic villi reside in a vascular niche. Placenta. 31(3):203-212

Betts DH, Kalionis B. (2010) Viable iPSC mice: A step closer to therapeutic applications in humans? Molecular Human Reproduction. 16(2):57-62

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