Urologic Conditions

Polycystic kidney disease (PKD) is a life-threatening and inherited disease, affecting 1 in 500 people. Patients with PKD have an abnormal proliferation of kidney cells that results in cyst formation and decline of kidney function. Autosomal dominant polycystic disease develops during adulthood, whereas autosomal recessive polycystic disease occurs in childhood, is rare, and often fatal.

PKD affects around 600,000 people in the United States. In a recent study, researchers were able to reprogram the skin cells in five patients with PKD. The cells change into pluripotent stem cells that gave rise to other cell types to repair kidney cells and delay kidney function deterioration.

Millions of people suffer with the painful bladder syndrome called interstitial cystitis. This debilitating condition causes an unpleasant sensation of pressure and pain, which is related to the urinary bladder and tract. The cause of IC is not known, but many people with the condition have the biomarker antiproliferative factor (APF) in their urine. This substance inhibits bladder cell proliferation, making bladder lining healing more difficult. Resent research shows that IC may be related to systemic neuroinflammation and neurosensitization that occurs within the bladder. In addition, the chronic inflammation results in damage to the bladder muscle and urothelium (lining of the urinary tract).

Mesenchymal stem cells are used to repair nerves, blood vessels, and urinary tract tissues. Adipose-derived stem cells recruited by cytokines are taken to the sites of inflammation and injury in the urinary tract. Stem cells are mobilized when they are activated following laboratory processing. A recent study using mice with bladder outlet obstruction was conducted. Mesenchymal stem cells were given intravenously to the test subjects, and researchers noticed decreased hypertrophy and fibrosis, as well as increased blood flow. These cells were given to patients with IC during different stages of the disease. Researchers found that intravesical instillation of ASCs effectively changed smooth muscle three months after instillation.

Peyronies Disease (PD) is a physically and psychologically devastating problem that is manifested by fibrous inelastic scars of the fibrous chambers of the penis, which is known as the tunica albuginea. This scarring causes pain, narrowing, bending, and shortening of the penis in an erect state. Recent studies show that around 9% of men have this problem, and it is more prevalent following radical prostatectomy surgery.

There is evidence that stem cells can seek out and attempt to repair the contracture associated with Peyronies plaques. Some patients with this condition are eligible to receive shock wave therapy along with stem cell treatment, which can activate stem cells, inducing healing and revascularization. The stem cell treatments aim to decrease fibrosis and scarring, so pain is lessened.

Male stress urinary incontinence affects many men following prostatic surgery. The incidence of male stress incontinence is around 20%, and it greatly affects quality of life. For some patients, surgery does not relieve the symptoms of male stress incontinence, which include sling procedures, artificial urinary sphincter implantation, and bulking agents. Stem cell injections and other therapies are now being used in the treatment of this condition.

In multiple animal model studies, researchers are studying the effect of stem cells in tissue regeneration of the urethra. In addition, stem cells derived from health tissue can be placed in the periurethral tissue to provide mucosal coaptation and restore resting urethral pressures of closing. Multipotent stem cells have been successful in rat subjects for treating stress incontinence. Investigations into the use of stem cells for this condition prove the therapy safe and effective.

Rat and pig subjects have been treated in clinical studies using stem cell therapy. The types of stem cells in these studies included:

• Bone marrow-derived stem cells (BMSCs) – The mesenchymal stem cells used for the regeneration of many muscular structures have demonstrated differentiation. With regard to regeneration of the urethral sphincter, the autologous BMSCs turned into striated muscle cells and peripheral nerve cells, which were damaged in the animal.
• Muscle-derived stem cells (MDSCs) – Found in muscle fibers, MDSCs can proliferate to form myoblasts, which create new muscle tissue. Studies have proven that MDSCs restore muscular contraction of the sphincter and recover damaged pelvic nerves. In addition, these cells improve urethral pressure and muscular myofibrils in the striated urinary sphincter of mice.
• Adipose-derived stem cells (ADSCs) – These cells can differentiate into myoblasts, fibroblasts, endothelial cells, and neurogenic cells. They can treat stress incontinence in animals by promoting nerve regeneration and improving resistance.

Recent research has utilized ADSCs in mice to study urological disorders with great promise for humans. For instance, florescent protein labeled mesenchymal stem cells were injected intravenously into mice that were suffering from bladder outlet obstruction. The result was decreased hypoxia, decreased hyportrophy, decreased fibrosis, and increased blood flow. Overall, 90% of the mice that received ADSCs experienced improved bladder compliance.

Thanks to studies that have been performed with mice, there is reason to believe that stem cell treatment will be helpful in treating interstitial cystitis in human patients. A protocol has been developed to treat various stages of IC with ADSCs by injecting stem cells intravenously, intra-vesically, and / or directly into trigger points in the pelvic floor. This protocol is supported by research where ADSCs were intravesically instilled into mice, which resulted in morphological and phenotypic improvements in the bladder wall.

In a study of 63 male patients who had stress incontinence after radical prostatectomy surgery, researchers found that stem cell therapy improved the condition, increased quality of life scores, and positively affected the thickness and contractility of the sphincter. The results supported that MDSCs could regenerate the urethral tissues and submucosa.

Lin CS & Lue TF (2013). Stem cells in urology: How far have we come? Nature Clinical Practice Urology, 5, 521.