Você está aqui


Treating Pelvic Organ Prolapse with Stem Cell Based Therapies

Novembro 2013
Caroline E. Gargett, PhD
Caroline E. Gargett, PhD

Caroline E. Gargett, PhD,
The Ritchie Centre,
Monash Institute of
Medical Research,
Melbourne, Australia

You might be asking "Just what is pelvic organ prolapse, or POP?" POP is when the bladder, and/or bowel, and/or uterus herniates into the vagina. Twenty five percent of all women have one or more symptoms of POP: urinary or bowel incontinence and sexual dysfunction - this is why it is a taboo subject - the symptoms are so embarrassing.

POP mainly results from pregnancy and injury associated with vaginal birth, particularly after prolonged second stage labour or the use of forceps. Delivering a large baby and having an episiotomy can also cause POP. POP is exacerbated by obesity, ageing, chronic coughing, heavy lifting and straining associated with constipation. Women who deliver their first baby over the age of 30 tend to have more severe POP.

Conservative treatment involves pelvic floor exercises, but in many cases surgical reconstruction (repair) operations are required. In fact 11-19% of women will have at least one operation for POP and 15-29% of these women will have multiple surgeries. Synthetic and biological mesh materials were rapidly introduced to provide extra support to the prolapsed pelvic tissues and to improve surgical outcomes.

While the use of mesh improved symptoms for many women, they have introduced another set of problems, often requiring their surgical removal if this is possible. The FDA has posted two warnings on the use of polypropylene mesh in vaginal surgery for POP, which has alerted clinicians to high rates (about 10%) of adverse events associated with their use. This has led to withdrawal from the market of several widely used brands of vaginal mesh, and looming class-action litigation. There is now a real risk that treatment options will become limited and ineffective again for large numbers of women.

We are investigating a potential stem cell-based therapy for POP using a tissue engineering approach rather than mesh alone. Our reasoning is that stem cells, particularly mesenchymal stem cells (MSCs), might assist in repairing the vaginal wall tissues that are damaged from childbirth injury.

The source of the MSCs for this tissue engineering approach is novel. We have discovered that the endometrial lining of the uterus which is shed and regenerates each month during menstruation contains a population of MSCs. These are easily collected from women via a biopsy in the doctor's office, without the need for any form of anaesthesia, in contrast to the collection procedures for bone marrow or fat sources of MSC stem cells.

Our techniques to purify these endometrial MSCs use magnetic beads and special markers, and we are currently working out protocols for growing them in culture to produce large numbers of cells under Good Manufacturing Practice (GMP) conditions. Our goal is to develop a stem cell-based therapy where women can use their own endometrial MSCs. The cells will be embedded in new, more patient-friendly, mesh materials that we have also been developing, that actually match the mechanical properties of human vaginal tissue.

We have demonstrated the proof-of-principle for this approach in an animal model that repaired wounds in the skin of rats. Our study showed that a tissue engineering construct comprising our new mesh and human endometrial MSCs significantly improved the mechanical properties of the mesh after a prolonged period of time (3 months). The endometrial MSCs appeared to exert their effect right from the beginning, by inducing the formation of new blood vessels around the implanted mesh, and altering the response of the body's immune system by promoting a wound healing effect rather than chronic inflammation. This in turn resulted in the laying down of new healthy collagen fibres through the mesh, in contrast to the mesh without cells where a thick scarring type of collagen formed.

The ability of the new mesh to grow healthy collagen fibres is important because it allows the new mesh to be more elastic and distensible, which addresses the key problem of currently used meshes and is the goal of our cell-based therapy.

Despite the millions of women in need of better treatment for POP, our ultimate goal is to prevent POP. We believe that if women are treated with their own MSCs soon after childbirth, using a less invasive introduction of cells, then their bodies will repair damaged pelvic floor muscles, vaginal walls, and ligaments years before POP has time to become severe enough to require reconstructive surgery. Clearly there is much research required before this goal can be achieved and the hidden disease burden of POP can be prevented.

Associate Professor Caroline Gargett is a Senior Research Fellow of the National Health and Medical Research Council of Australia, and Deputy Director of the Ritchie Centre at Monash Institute of Medical Research, Melbourne Australia, where she heads Women's Health. She is also a member of Monash University's Department of Obstetrics and Gynaecology. Dr Gargett obtained her PhD in 1997 and became an independent researcher in 2004 when she discovered adult stem cells in the lining of the uterus (endometrium). She leads a research group of 8-12 staff and students and her research focuses on examining the role of endometrial stem cells in endometriosis. She is also developing novel approaches for treating pelvic organ prolapse using endometrial stem cells and new materials in collaboration with Materials Scientists and Tissue Engineers from CSIRO, Australia's leading Scientific and Industrial Research Organisation. She is President of the Australasian Society for Stem Cell Research and is on the Editorial Boards of Reproductive Sciences, Fertility and Sterility and Biology of Reproduction.