Hudson Institute scientists have demonstrated a two-step stem cell-based bioengineering approach in a pre-clinical model for the treatment of pelvic organ prolapse (POP).
POP is an unglamorous disease, which people often feel uncomfortable discussing. Despite it affecting one in four women worldwide, and up to 60 percent of mothers over the age of 50, many also remain unaware of the condition.
What is POP?
When the muscles, tissues and ligaments supporting the pelvic organs (the uterus, bladder and bowel) are weakened or damaged-usually due to childbirth-POP can develop and cause one or more of the pelvic organs to drop/push into, or even outside of the vagina.
Difficulty in emptying the bladder or bowel, back pain and pain during sex are just some of the debilitating symptoms women may suffer.
There is currently no optimal treatment for POP, due to the banning of non-degradable, polypropylene transvaginal meshes by several countries, including Australia, New Zealand, UK and USA. These meshes caused some women detrimental complications such as exposure (protrusion into the bladder or bowel), erosion into the vagina, chronic pain and inability to have sex.
Other non-surgical treatment options such as pessaries and pelvic floor exercises are available, yet they do not stop POP progression. Women with POP who require surgery (one in five) are either offered native tissue surgery which has a high failure rate, or abdominal surgery which is highly invasive.
A collaborative approach
Hudson Institute researchers have spent nine years striving to find a safe and effective treatment option for women with POP. A study published in Biomaterials led by PhD student Stuart Emmerson and Professor Caroline Gargett, investigated a cell-based bioengineering approach with several key collaborators-including urogynaecologist Anna Rosamilia from Monash Health and researchers from CSIRO.
The team compared two different methods of implanting autologous endometrial stem cells (from the uterus lining) and a purpose-designed nylon mesh into a pre-clinical model, which closely reflected a woman with POP.
The first, one-step method involved combining the stem cells and the nylon mesh (coated in a gel), and then trialling the premade construct. The second method involved a two-step process, in which the uncoated mesh was inserted alone, followed by the stem cells, which were coated in a gel.
One-step or two-step?
The researchers discovered that the second, two-step method led to better tissue integration, less smooth muscle disruption and less loss of elastin fibres in comparison to the first method.
The first method led to mesh folding, poor tissue integration and mesh exposure-uncovering a problem that didn't occur in previous models, similar to the detrimental complications of the banned meshes and would be extremely damaging to women. By closely reflecting a woman with POP, the representative model was more sensitive in detecting problems than in previous studies.
The uncoated mesh used in the second method had greater drapeability, meaning it was less stiff than the coated mesh, and the team believe this led to the positive results. The two-step method was also found to be a simpler, surgically easier process.
"Our authentic pre-clinical POP vaginal surgery model offers an improved approach for evaluating the new bioengineered therapies we are developing to fill the void since the banning of transvaginal mesh" said Professor Gargett.
"Our hope is that our cell-based therapy together with new mesh designed specifically for transvaginal surgery will provide a safe and durable treatment for the millions of women with POP."
Future outlook
Stem cells were still present after 30 days (more than double the survival time in previous models), reducing the inflammatory response and promoting blood vessel growth. These promising results show the potential of using individuals' own stem cells in POP treatment-an autologous approach.
The team are now looking to conduct longer-term studies in the same models, with meshes made of degradable material. Research led by Hudson Institute's Kallyanashis Paul and Dr Shayanti Mukherjee has demonstrated how this type of mesh could help overcome current challenges faced in POP treatment.
Applying learnings from each POP study will help to discover an effective and safe treatment option for millions of women worldwide.
Collaborators
Anna Rosamilia of the Pelvic Floor Disorders unit, Monash Health; International urogynaecology Fellows, Monash Health; CSIRO; A*Star Singapore.
Funders
NHMRC.
