The role of the identified regulators of cell fate (RCF) and metastasis-inducing-proteins (MIP) in endometrial stem/progenitor cells (SPC) in endometriosis.
Dr Dharani Hapangama (Liverpool Women’s Hospital), Dr Caroline Gargett, Professor Philip S Rudland, Dr Gabriele Saretzki, Professor Thomas von Zglinicki, Dr Siobhan Quenby
£149,247 over 36 months
LAY TITLE: Study of the importance of stem cells from the human womb lining in establishing endometriosis to formulate/propose new treatments
Endometriosis affects 1 in 10 women below the age of 50, which equates to over 5 million in the UK. These women experience severe pelvic pain, period pains, painful sexual intercourse and infertility. Endometriosis is also associated with absence from work and failure to conceive. Diagnosis requires invasive techniques and hospital admission, and currently available medical treatments have many side effects and only provide temporary relief in a minority of sufferers. Many women undergo risky, extensive and repeated surgery but even the removal of their ovaries and uterus may not cure them fully of their symptoms.
Estimates from the year 2000 indicate that endometriosis directly costs UK society and the NHS over £2 billion per year. The lack of a simple diagnostic test results in delayed diagnosis / treatment with personal/ economic consequences. Little is known about why women develop endometriosis, the mechanisms by which endometriosis develops or its natural progression. These factors have hindered the development of preventative strategies and new effective treatments acceptable to all women suffering with the disease.
Endometriosis occurs when cells of the inner lining of the womb are found growing outside of the uterus. At the time of a woman’s menstruation these cells, called endometrial cells, are shed from the womb lining and can be expelled into the abdominal cavity. If these cells continue to live, attach and are implanted in the pelvis and abdomen they can cause severe pain and in serious cases can lead to infertility.
We think that the stem cells from the lining of the womb are inappropriately shed in to the pelvis and that they have an abnormally high capacity to proliferate, survive and metastasise in women with endometriosis, so these cells are likely to give rise to endometriosis lesions. This application therefore, aims to extend our previous work defining the role of the controllers of cell fate and metastasis to determine their possible role in endometrial stem/progenitor cells. The proposed research will provide new insights into the mechanisms involved in normal growth of endometrium in healthy women and abnormal endometrial growth associated with endometriosis. It may also provide new markers in these cells to develop non-invasive tests for diagnosis and new targets to develop more effective treatments to improve the health and quality of life of large numbers of young women suffering with endometriosis.
Endometriotic cells often have properties of motility and invasiveness, the investigation of which may also improve our knowledge of malignant cell biology.