Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Uterine stem cell isolation and functions (#11)

Caroline E Gargett 1 2
  1. Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia
  2. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia

Stem/progenitor cells were discovered 12 years ago in the human uterine lining (endometrium) as clonogenic cells1. There has been little characterisation of endometrial epithelial progenitor cells. In contrast, endometrial mesenchymal stem/stromal cells (eMSC) are now well characterised, showing similar properties to bone marrow MSC; clonogenicity, multi-lineage differentiation (adipose, cartilage, bone) and express phenotypic surface markers. More specific markers purifying eMSC have been identified; co-expression of PDGFRβ and CD1462, and single marker SUSD23, which revealed eMSC identity as pericytes/perivascular cells in vivo. EMSC reconstituted stromal tissue when xenografted into mice.

Mesenchmal stem/stromal cells (MSC) are attractive for cell-based therapies to repair tissues such as bone, cartilage and heart muscle. Their non-stem cell anti-inflammatory, immunomodulatory and trophic properties have also been exploited in clinical trials for chronic disorders including Crohn’s and Graft-Vs-Host diseases. While preclinical models have demonstrated efficacy of MSC, the outcome of many clinical trials has been underwhelming for various reasons. The MSC administered are heterogeneous, predominantly comprising stromal fibroblasts, as purification of pericyte populations is rarely done. MSC usually require expansion in culture to generate sufficient numbers for transplantation, but they spontaneously differentiate. The commercially favoured approach is allogeneic but increasing evidence indicates MSC elicit an immune response, thus limiting them to a single use. MSC are mainly given intravenously and become trapped in the lungs where they elicit a systemic cytokine response and are cleared within 24-48 hours. In the rush to the clinic, few studies on MSC mechanism of action have been undertaken.

Endometrial MSC can be obtained without an anaesthetic, which is required for bone marrow and adipose tissue MSC. We use our markers to enrich for pericytes/perivascular cells, and a TGFβ-receptor inhibitor (A83-01) during eMSC culture expansion to overcome spontaneous differentiation4. In our preclinical model we are testing autologous ovine eMSC delivered directly to the site of injury and we examine mechanism of action to ensure future success of eMSC as a cell-based therapy.

  1. Chan RW, Schwab KE & Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. 2004 Biol Reprod 70: 1738-50.
  2. Schwab KE & Gargett CE. Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. 2007 Hum Reprod 22: 2903-11.
  3. Masuda H, Anwar SS, Buhring HJ, Rao JR & Gargett CE. A novel marker of human endometrial mesenchymal stem-like cells. 2012 Cell Transplant 21: 2201-14.
  4. Gurung S, Werkmeister JA & Gargett CE. Inhibition of Transforming Growth Factor-beta Receptor signaling promotes culture expansion of undifferentiated human Endometrial Mesenchymal Stem/stromal Cells. 2015 Sci Rep 5: 15042.