Marrow stem cells used to regenerate bladder function

Atlanta-Marrow stem cells may one day be used to cure incontinence by reconstructing the sphincter, new research from Germany suggests.

"We are aging. We are losing muscle tissue. So if we can bring back smooth and striated muscle cells, we can regenerate the function," said researcher Karl-Dietrich Sievert, MD, associate professor and director of reconstructive and neuro-urology at the University of Tübingen. "Bulking agents, as we all know, work in most people, but for a limited time. If you can have reconstruction of this function, then you are much better off."

That's the goal of the research team led by Dr. Sievert, who presented results from early animal research on their technique at the AUA annual meeting here. The investigators harvested mesenchymal stem cells from rat bone marrow and induced them to differentiate. Ultimately, the team hopes to use methods that would be much easier on patients than bone marrow harvesting, or even muscle biopsy, and would also yield the desired types of cells.

"We think we can differentiate the cells better," said Dr. Sievert, comparing this technique with culturing cells from muscle biopsy specimens. "We are taking cells at an earlier point, and we are able to manipulate them better to get the cell type we want more."

Which cells you want, he explained, depends on where you want to inject them.

In the current study, the team prompted the mesenchymal stem cells to differentiate by exposing cultures to 5-azacytidine. Then, using immunohistochemical techniques with antibodies to smooth muscle alpha-actin, skeletal muscle MyoD, and skeletal slow muscle myosin, they tested the resulting cell mix for these cell types. The cultured cells were mostly smooth muscle. The team saw positive reactions with both anti-smooth muscle alpha-actin antibodies, but detected only single cells with skeletal muscle antibodies.

Cell migration seen

The researchers then injected these differentiated cells labeled with a fluorescent marker into the bladder neck of rats and tracked the cells over time, monitoring them histologically at 2, 4, 7, 45, and 128 days after injection.

"We were surprised that we didn't have cells only in one location as injected," Dr. Sievert said. "After a while, they appeared in the whole circumference of the bladder neck."

And that was not just because of diffusion of stain, he explained, which would have appeared as a halo. Instead, the team saw nests of cells form in the muscle layers, and then the cells became equally distributed around the bladder neck. The cells were, in fact, migrating, indicating that functional regeneration was taking place.

The research team will be taking the next steps in this research, testing techniques in larger animals and starting parallel human trials with an aim for regulatory approvals in the United States and Europe.