Endometrial Stem Cell Biology

Endometrial Stem Cell Biology Research Group

Research Group Head

Following the group’s discovery of endometrial stem/progenitor cells in the highly regenerative lining of the uterus (endometrium), the Endometrial Stem Cell Biology research team has focused on characterising endometrial stem/progenitor cells and their role in gynaecological disease. The group also discovered markers of the epithelial progenitors and mesenchymal stem/stromal cells (MSC) found in human, ovine and mouse endometrium, enabling us to investigate:

  • Basic cellular and molecular biology of human and mouse endometrial stem/progenitor cells.
    • The mouse model uses transgenic telomerase reporter mice (m-Tert-GFP) to identify and study the function of mouse endometrial stem/progenitor cells. A Cre version is used for lineage tracing.
    • the use of 3D organoid cultures to investigate the properties and signalling pathways used by human and mouse endometrial epithelial progenitor cells.
  • The utility of endometrial MSC combined with novel scaffold materials developed with CSIRO collaborators as a cell-based therapy for treating Pelvic Organ Prolapse. This extremely common condition results from herniation of pelvic organs into the vagina due to childbirth injury. Our tissue engineering approach for vaginal surgical repair shows promise in a rat model and we are assessing their utility in a sheep vaginal surgery model for preclinical studies. This interdisciplinary research also includes the following
    • the development of a secondary prevention strategy for treating women soon after childbirth with their own endometrial MSC and novel nanobiomaterials for local delivery of cells to prevent Pelvic Organ Prolapse occurring later in life.
    • using small molecules to maintain stemness of endometrial MSC and produce a reproducible cell product for clinical use. Combined RNAseq and ATACseq is being used to discover mechanism and the research is being applied to placental, menstrual blood and bone marrow MSC
    • The immunomodulatory properties of human endometrial MSC. Similar to bone marrow MSC, endometrial MSC show anti-inflammatory, immunomodulatory properties and promote wound healing in culture and in mouse and ovine models
    • Development of a novel pressure sensor device using fibre optics technology by collaborators from Flinders University which is currently being trialled in women to more precisely diagnose areas of vaginal wall weakness.
    • In collaboration with modellers, engineers and material scientists at CSIRO and Monash Institute of Medical Engineering, the team is undertaking the rational design of mesh materials for use in Pelvic Organ Prolapse surgery that better matches vaginal tissue biomechanical properties
  • Whether endometrial stem/progenitor cells shed in menstrual blood gain access to the pelvic cavity during retrograde menstruation, where they establish endometriosis. This serious chronic disease affects 10% of young women where endometrial tissue grows outside the uterus. It causes severe pain and infertility and current treatments are suboptimal.
    • RNAseq on purified populations of endometrial stem/progenitor cells is being examined to identify differences between women with endometriosis that allow the stem/progenitor cells to implant and grow in the pelvis and normal women.
    • using the mTert-GFP mouse, a model of endometriosis mimicking the attachment of menstrual debris to the peritoneum has been established to examine the role of stem cell signalling pathways in establishing lesions
    • other studies are assessing whether neonatal uterine bleeding is a potential biomarker of adolescent endometriosis.
  • Endometrial-related infertility where the endometrium fails to support embryo implantation particularly in women with Recurrent Implantation Failure undergoing IVF procedures. The role of endometrial stem/ progenitor cells is under investigation.

Research Projects:

  • How does the endometrium regenerate? Role of the Wnt signalling pathway.
  • Testing the in vivo regenerative potential of human endometrial epithelial progenitor cells isolated using a new marker
  • Do human endometrial mesenchymal stem/stromal cells (MSC) have immunomodulatory properties that can be harnessed for treatment of human disease?
  • Developing protocols for cell production of autologous endometrial MSC in preparation for clinical use.
  • Role of endometrial stem/progenitor cells in endometriosis
  • Role of endometrial stem/progenitor cells in endometrial injury-induced doubling of pregnancy rates in women with Recurrent Implantation Failure undergoing IVF
  • Developing a large animal preclinical model of birth-induced injury to assess the efficacy of autologous endometrial MSC as a cell based therapy to prevent Pelvic Organ Prolapse
  • Nanotechnology and tissue engineering strategies to uncover causes and treat Pelvic Floor Disorders
  • Investigating the requirement for Notch and Hedgehog signalling in the endometrial stem/progenitor populations that cause endometriosis
  • Organoids from mouse and human endometrial stem/progenitor cell populations

 

Research Group