PAINFUL BLADDER SYNDROME
Millions of patients suffer from Interstitial Cystitis /painful bladder syndrome. This severe and debilitating condition has historically been confused with other bladder pathology which must be ruled out, making IC difficult to diagnose. Currently, Interstitial Cystitis/PBS is defined as “an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes.” (2009 new American IC/BPS Guidelines). Although there are several theories to explain IC, the exact cause remains unclear. Many patients with IC have the biomarker APF (antiproliferative factor) in their urine which inhibits bladder cell proliferation, making healing of the bladder lining much more difficult (1). Recent research indicates IC may be related to systemic neurosensitization and neuroinflammation that occurs within the bladder and also some other organ systems (2). Regardless of the cause, the end result of IC is damage to urothelium and bladder muscle that can run the spectrum from mild mucosal irritation to deep Hunner’s ulcers.
INTERSTITIAL CYSTITIS AND ADIPOSE DERIVED MESENCHYMAL STEM CELLS
Adipose derived adult (non-embryonic) mesenchymal stem cells are currently being investigated for use in degenerative conditions that result in damage to various organs and systems. These cells have the ability to seek out areas of injury and regeneration and assist in the repair of nerves, blood vessels, muscle, fat, cartilage, bone, and many other structures. These cells are naturally recruited by cytokines (SDF-1 stromal derived factor one, HGF hepatocyte growth factor, and platelets), to sites of inflammation, ischemia, hypoxia, or injury and they assist in the healing process either by directly forming needed cells or secreting chemical messengers that promote healing. Stem cells are mobilized naturally from bone marrow when the body is healing but they are also found dormant but available in human adipose tissue. These stem cells from fat are abundant in levels up to 2500 times greater than those found in bone marrow and research indicates that the fat derived stem cells have equivalent regeneration potential to the bone marrow cells (3). Also, stem cell treatment success appears to relate to the number of cells used and this gives adipose cells a significant potential advantage to regenerate human tissues. Mesenchymal stem cells have been used extensively around the world in the successful treatment of orthopedic, cardiac, pulmonary, and neurologic disease in both humans and veterinary models. We have evidence that adipose derived stem cells can differentiate into functional smooth muscle cells (4,5) and we think therefore, that bladder repair by stem cells may be possible in IC patients. A recent study in mice with bladder outlet obstruction demonstrated that florescent protein labeled MSC’s (mesenchymal stem cells) injected intravenously into test subjects incorporated into bladder muscle resulting in decreased hypoxia, hypertrophy, and fibrosis and increased blood flow. Nine out of ten mice who received MSC’s had improved bladder compliance (6).
We know that patients with IC demonstrate abnormal cell signaling and cytokine release (7). For this reason, we believe that stem cell treatment may be helpful for interstitial cystitis patients who exhibit mucosal and smooth muscular damage. We have developed a protocol to treat patients with IC of various stages with adipose derived stem cells. Our protocol uses high doses of stem cells injected intravenously and also intra-vesically (directly into the bladder lumen) and in some cases directly into trigger points in the pelvic floor. We have evidence that intravesical instillation of adipose derived stem cells into mice effectively shows morphological and phenotypic evidence of smooth muscle incorporation into the bladder wall three months after instillation (8).
Cell Surgical Network Center is using high dose autologous adipose derived stem cells for the investigational treatment of various degenerative diseases. The use of autologous cells ensures that the patients receive cells from only their own bodies. The technology to isolate the adipose derived stem cells has been obtained from Korea and is state of the art. All studies are patient funded and not approved by the FDA. We have initiated a pilot study to investigate the effectiveness of high dose adipose derived stem cells on interstitial cystitis. Only adult adipose derived stem cells are used at the Cell Surgical Network since embryonic stem cells have the potential to form rare tumors and have ethical considerations. At Cell Surgical Netowrk, the stem cells are obtained from a “mini” liposuction-like procedure performed under local anesthetic. Stem cells are isolated on site from the patient’s own fat and then deployed in our facility within 90 minutes. Regenerative healing naturally takes time and we do not expect immediate improvement in symptoms. Patients will be followed closely through our research registry and data collected carefully to help establish effectiveness of our treatment protocols.