Human Amniotic Stem Cells Treat Stress Urinary Incontinence in Animals

Stress Urinary Incontinence (SUI) refers to the involuntary leakage of urine during physical activity, sneezing, or coughing. This is an extremely embarrassing problem for women and some men. Treatments for this condition includes various types of tapes (tension free vaginal tape) and slings (transobturator slings or pubovaginal slings) can help somewhat. Nonsurgical treatments include bulking agents (polytetrafluoroethylene, bovine collagen, silicone particles, carbon beads, and autologous fat or chondrocytes. The non-surgical procedures have only had limited success, and even the present surgical procedures are largely unsatisfactory.

Therefore, to design better treatments for SUI, researchers have turned to stem cells. In this present paper, Bum Soo Kim and his colleagues from the Departments of Urology, Physiology, Plastic and Reconstructive Surgery in the School of Medicine at Kyungpook National University in Daegu, South Korea, in collaboration with Anthony Atala from the Wake Forest University of Medicine in Winston-Salem, North Carolina have injected human amniotic stem cells into the urethras of laboratory animals with SUI. Their results are very positive and interesting.

Mice can be given SUI by means of bisecting the nerve bundle (pudendal nerve) that serves the urethra. By crushing this nerve bundle, the mice lose control of their bladders and show all the signs of SUI.

One week after the mice were confirmed have SUI, they were given an injection of about half a million human amniotic stem cells into the muscle that cinches down the urethra. Cells were injected into either side of the urethral sphincter muscle. The injected cells were labeled with tiny dye-laced beads to watch them during their sojourn inside the animals.

Measurements of the bladder control of the injected mice was determined with a catheter that measured LPP or leak point pressure and the closing pressure or CP. After these measurements, the animals were sacrificed and their bladders were examined to determine if the injected stem cells integrated into urethral sphincter.

The results showed that the injected cells had the characteristics of mesenchymal stem cells. In culture, they were able to differentiate into smooth muscle tissue.

In the laboratory animals, the injected cells had migrated into the urethral sphincter and surrounded it. Optical tracking injected cells showed that they were alive and localized in the urethral area. LPP and CP measurements also showed that these measurements were significantly higher in the injected animals 2 weeks and 4 weeks after stem cell injections relative to those animals that were not injected.

Tissue sampling of the urethral sphincters from injected animals showed that the sphincter muscles were loaded with dye-containing beads, indicating that the injected amniotic stem cells integrated into the sphincter muscle and stayed there.  Secondly, the cells expressed a boat-load of genes involved in the formation of muscle (PAX7, MYF5 and
MYOD), and MYOGENIN, MEF2 and MLP).  They also expressed genes that encode proteins that allow smooth muscle cells to respond to impulses from nerve cells.  This shows that the injected cells responded to the environment into which they were placed and differentiated accordingly, in this case, into smooth muscle.  Also, none of the injected animals showed any signs of rejection of the injected stem cells by the immune system.  Also, none of the animals showed any tumors from the injected stem cells.

This study shows several positive results.  First of all, the injected amniotic stem cells were able to nicely survive in the urethral sphincter.  Secondly, they were not rejected by the host immune system and did not form tumors.  Third, these cells also differentiated into smooth muscle cells and properly integrated into the urethral sphincter muscle.  Finally, these cells partially restored function to the urethral sphincter.

Is this procedure feasible in humans?  In theory, it is certainly possible.  Injections into the human urethral sphincter are difficult and require high resolution imaging procedures to properly guide the physician during the injection.  High resolution MRI-guided injections are possible, but this exposes the patient to large quantities of radiation.   This present paper shows that it is entirely possible to mark the cells in a manner that is not toxic to them in order to properly trace the injected cells.  Such labeling would allow physicians to deliver the cells with lower-resolution techniques that do not expose the patient to such high levels of radiation.

This paper provides a remarkable example of how non-embryonic stem cells can provide a treatment for a troublesome and embarrassing medical problem.  The paper is Bum Soo Kim, et al.,  “Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model,” BMC Medicine 2012, 10:94 doi:10.1186/1741-7015-10-94.