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Atlanta-Autologous adipose stem cells lend themselves well to the engineering of bladder smooth muscle and may eventually make the use of gastrointestinal tissue for this purpose obsolete, say researchers from UCLA.
The group reported at the AUA annual meeting that it has shown, for the first time, that adipose stem cells can be differentiated into functional smooth muscle.
"The advantage of using stem cells is that they are pluripotent and capable of forming multiple tissue types, including smooth muscle," said lead author Larissa V. Rodríguez, MD, assistant professor of urology. "The particular advantage of using adipose stem cells is that it makes this an autologous model, and therefore there is no need for immunosuppression.
Dr. Rodríguez, first author Gregory S. Jack, MD, and colleagues processed adipose stem cells (ASCs) from human lipospirate. ASCs were then differentiated into smooth muscle phenotype (SM-ASCs) using smooth muscle-inductive cultured media.
The group formed a three-dimensional scaffold using poly-latic-glycolic acid molded from electropulled microfibers layered under a porous sponge. Some scaffolds were seeded with SM-ASCs, while others were left unseeded.
A group of 45 female nude rats underwent laparotomy, removal of bladder dome, and repair using one of three methods:
Follow-up was conducted at regular times over a 12-week period postoperatively using bladder cystometry, isometric studies, and histology.
Good results at follow-up
The rats with engineered tissue maintained smooth muscle mRNA and protein in vitro, along with bladder capacity and compliance at all follow-up points in vivo, the researchers reported. Animals given unseeded scaffold, meanwhile, lost capacity over time and experienced poor compliance. Lower bladder volume was also seen in the cystectomy group.
"In addition to the ability of these cells to form smooth muscle, our work was also novel because it showed that engineered bladder tissue could contract as native bladder," Dr. Rodríguez said.
Indeed, isometric tissue baths showed dose-dependent contraction of tissue-engineered grafts with carbachol. Unseeded grafts were unresponsive in this respect.
What's more, 12 weeks after implantation, the smooth-muscle adipose stem cells "expressed smooth muscle action and myosin heavy chain," the authors noted.
Using autologous smooth muscle cells obtained from bladder biopsies to engineer bladder tissue is associated with its share of difficulties, Dr. Rodríguez noted.
"Not only do cells need to be expanded in culture for multiple passages, but most patients who require a neobladder or bladder tissue are experiencing underlying bladder pathology (cancer or neurogenic disease), and it has been shown that pathologic bladders lead to pathologic smooth muscle cells," she said.
Dr. Rodríguez and colleagues also presented a paper here describing the successful use of SM-ASCs to treat urethral resistance and function by restoring smooth muscle contractility in patients with stress incontinence.
The paper won the AUA/Gyrus ACMI Prize Essay Contest in the Laboratory Research category.