New connective tissue for the pelvic floor

New connective tissue

for the pelvic floor

Menglin Chen is the principal architect behind the new nanofibres that can be used as scaffold for stem cells in the body. Photo: Maria Randima.

Researchers at Aarhus University have got stem cells to form new connective tissue by giving them scaffolding materials to work on. There are great perspectives for treating tissue injuries such as prolapse of the reproductive organs in women.

The scaffold is thin and soft and readily breaks down in the body. This sounds like a case for the health and safety authorities, but so far the scaffold has proved to be safe and effective.

“However, we’ll have to complete many more trials before the scaffold can be used in human beings. We’re still in the process of testing it on mice and rats,” says Assistant Professor Menglin Chen.

She is in the research group, which has recently published news of an important breakthrough in stem cells to form new connective tissue by means of scaffolds built of nanofibres.

Connective tissue does not readily heal
In principle, stem cells can develop into any type of cells in the body. The problem is to get them to do so on command: to get them to create new and healthy versions of specific cells that, due to injury, illness, age or pregnancy, no longer function as they should.

“Many women injure the connective tissue in the pelvic region when they give birth. And that’s not good because the cells, which make up the main component of the connective tissue, are not good at repairing themselves when they’ve been damaged,” says Menglin Chen.

Furthermore, connective tissue weakens with age, and there are fewer and fewer of them.

Almost 20 per cent of all women – and up to 50 per cent of all women over the age of 50 – in the industrialised world suffer prolapse of the reproductive organs, because the connective tissue in their pelvic floor is weakened.

Fibres replace bad implants
In addition to the general discomfort, prolapse of the reproductive organs can also lead to incontinence. Many women have an operation, but the existing options are not particularly reliable. Stitches in the weak connective tissue are not very strong, so the risk of relapse is up to 30 per cent.

Furthermore, the implants of synthetic meshes used today have in many cases proven to do more harm than good because they can easily perforate the healthy tissue. In the US, use of these meshes has resulted in tens of thousands of actions for damages.

“So it’s crucial that we find an alternative that does not damage the tissue and has no complications: preferably something that supports the patient’s own tissue. It’d be brilliant if we could get the patient’s own connective tissue cells to grow,” explains Susanne Maigaard Axelsen, a consultant physician taking part in the development work at the Department of Clinical Medicine, Department of Gynecology and Obstetrics at Aarhus University Hospital.

Electrospinning with great health potential
The researchers have used electrospinning to create a scaffolding of biodegradable nanofibres that mimics the extracellular matrix – i.e. the structure that holds the cells together and supports the tissue.

The fibres have been provided with hydrogel and growth factors, which are signal molecules that initiate the processes that cause the stem cells to develop in the direction desired.

The whole thing is as thin and flexible as silk paper (actually it looks a lot like paper) but strong enough to be sewn onto the living tissue.

“We’ve got the stem cells to attach themselves to the scaffold and start forming new fibroblastic connective tissue. So far, we’ve got it to work with human stem cells in mice and rats, but the test animals are very small and walk on four legs, so they can’t be used as models for how it would work in humans. We’d like to test it on larger animals such as pigs and sheep,” says Menglin Chen.

In the current case, the researchers have used normal skin cells, which, by means of genetic engineering, have been ‘back-programmed’ to behave like stem cells - so-called induced pluripotent stem cells (iPSC), which can be influenced to become virtually any type of cell in the human organism.

The researchers have been working closely with Coloplast on the new pelvic- floor implants. Coloplast already has sharp focus on the treatment of incontinence. The Danish Council for Strategic Research has invested DKK 10 million in the project, which has now achieved promising results.