Feline idiopathic cystitis (FIC) is a bladder disorder of unknown cause that affects a quarter to a half million cats annually in North America. It is the most common urinary disorder of young to middle-aged cats and is characterized by frequent, bloody, and painful urinations, house-soiling, and in some cases, life-threatening urinary obstruction. Symptoms often subside within about a week in most cats. However, there are many cats who experience a more severe form of idiopathic cystitis in which symptoms persist for weeks to months or frequently recur. These cats are classified as having chronic idiopathic cystitis.

Unfortunately, there is no consistently effective means of treatment and prevention of chronic idiopathic cystitis. The failure of attempts to treat chronic idiopathic cystitis is often the reason that many affected cats are surrendered, abandoned, or euthanatized. Consequently, there is a critical need for alternative forms of therapy that would maximize the likelihood of successful management and prevention of chronic idiopathic cystitis.

Generally, symptoms of idiopathic cystitis include varying combinations of the following:

• Increased frequency of urination
• House-soiling or urination outside of the litter box
• Painful urination
• Bloody urine
• Straining to urinate

An inability to urinate (urinary obstruction) is a serious and potentially life-threatening complication encountered in some cats with FIC.

Unfortunately, there is no specific single diagnostic test or marker that establishes a diagnosis of idiopathic cystitis. Diagnosis requires appropriate evaluations to exclude other disorders that cause similar symptoms, such as bladder stones, bacterial infections, bladder tumors, or behavioral disorders. Evaluation often involves collection of a urine specimen for urinalysis and bacterial culture, and imaging of the urinary system with ultrasound, x-ray studies, or urethrocystoscopy.

In the past decade, over 80 agents or procedures have been recommended for management of idiopathic cystitis in cats; yet, fewer than 10% of these proposed treatments have been evaluated in controlled clinical trials. Treatment recommendations for cats with chronic idiopathic cystitis often include dietary, environmental, pharmacologic, and behavioral interventions; but unfortunately, none of these therapies have been consistently effective for management of cats with chronic idiopathic cystitis. Clearly there is a needed for alternative therapies that can provide consistent long-term control of symptoms associated with chronic idiopathic cystitis.

Mesenchymal Stem Cell Research Project Description

Adult mesenchymal stem cells are special self-renewing progenitor cells that are capable of differentiating into more specific cell types. Fat tissue is one of the richest sources of mesenchymal stem cells in adult animals. While initial interest focused on use of mesenchymal stem cells for tissue regeneration, it is now apparent that mesenchymal stem cells are endowed with remarkable immunomodulatory properties that are likely responsible for promoting tissue healing and repair. This unique characteristic has lead to their use for treatment of chronic inflammatory diseases in people and animals. Chronic inflammation is a common finding in bladder biopsies of cats with chronic idiopathic cystitis. Infiltration of the bladder wall by cells that mediate inflammation and regulate the immune system is probably an important causative factor for the symptoms seen in this disease.

We hypothesize that mesenchymal stem cell therapy will be beneficial for cats with chronic idiopathic cystitis. The goal of our study is to investigate the efficacy of intraperitoneal injection of autologous fat tissue-derived mesenchymal stem cells in cats with severe chronic idiopathic cystitis that have failed conventional therapies. What this means is that we will use the affected cat's own stem cells isolated from its own fat tissue to treat the disease. A small amount of fat tissue will be collected from just under the skin from each cat, through a small incision, under anesthesia. The mesencymal stem cells will be purified from the fat, “tagged” with nanoparticles, and given back to the patient by injection into the abdominal cavity under general anesthesia and with ultrasound guidance. This route of administration is designed to place the stem cells in close proximity to the bladder to ensure that the stem cells can reach the intended target. Results of recent safety studies in healthy cats indicate that this route of stem cell administration is safe and not associated with any major side effects. As part of the study we will also track migration of the stem cells after injection using MRI. MRI scans will be performed immediately before and after stem cell injection, and again one week after injection.

The measure of success of stem cell therapy will be based on the number and frequency of bladder symptoms before and after treatment. Our study design is unique in that each cat will receive stem cell therapy and that each cat will serve as its own control. Each cat’s symptoms will be quantified for approximately 2 months prior to stem cell injection. The same symptoms will then quantified in each cat for 6 months after stem cell injection and compared to the baseline data. It is our expectation that administration of mesenchymal stem cell to cats with chronic idiopathic cystitis will significantly reduce the frequency and severity of symptoms associated with this disease.