Interstitial Cystitis/Painful Bladder Syndrome
 

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).

     We are 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 Network, 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.

 
CANDIDATE APPLICATION
RESOURCES

Cell Surgical Network Study for Stromal Vascular Fraction Registered by ClinicalTrials.gov

Rancho Mirage, CA (PRWEB) October 14, 2013

Clinicaltrials.gov, a service of the U.S. National Institutes of Health has registered on their public site an IRB approved safety study from the Cell Surgical Network, Inc.. This study is available for patients with various degenerative and inflammatory conditions to undergo Stromal Vascular Fraction deployment for the evaluation and for the advancement of future stem cell therapy procedures. Stromal Vascular Fraction is rich in autologous adipose derived stem cells and growth factors.

Stromal Vascular Fraction (SVF) is obtained by lipo-harvesting, procurement, and lipo-transfer as a same day operative procedure to provide therapy to patients with various degenerative and inflammatory diseases. Patients must be 16 years or older, male or female and have a degenerative disease or inflammatory disease that meets criteria for treatment under the IRB which includes: Arthritis, Auto-immune disease, COPD, Cardiomyopathy, Peyronies Disease, Interstitial Cystitis, Erectile Dysfunction, and Neurodegenerative disease such as Parkinson’s, ALS, Neuropathy. Patients must be healthy enough to tolerate a local anesthetic, must not have active cancer or infections.

Dr. Elliot Lander, and Dr. Mark Berman, founders of the Cell Surgical Network Inc. will conduct the study: “Ever since our inception, it’s been our goal to maintain transparency during our investigations. With a closed surgical procedure we can provide effective safety studies and evolve good empirical data that will allow us and others to ultimately refine our protocols,” says Dr. Berman.

The purpose of the safety study is to evaluate for any adverse effects that may be related to the administration and reception of autologous adipose derived stromal vascular fraction (SVF). Secondarily, the study monitors the results of subjective and objective findings as it applies to the non-blinded deployment of autologous SVF for various inflammatory and/or degenerative conditions including select orthopedic, neurologic, urologic and cardio-pulmonary conditions. SVF deployments include intra-venous, intra-articular, and soft tissue injections.

Outcome measures will include the number of participants with adverse events related to either SVF deployment or the lipo-harvesting procedure. Interested patients should contact the treatment center by phone: 800-231-0407 or via email: info(at)cellsurgicalnetwork(dot)com

About Cell Surgical Network:

The affiliates of the Cell Surgical Network (CSN) are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions. The Cell Surgical Network was founded nearly two years after the formation of the California Stem Cell Treatment Center (founded in 2010). Affiliate members are generally made up of multi-state and international teams of multidisciplinary physicians in order to best assess and provide care for our patients. The Cell Surgical Network emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine.

 

Stem Cell Therapy for Interstitial Cystitis/Bladder Pain Syndrome.
 


 Curr Urol Rep. 2016 Jan;17(1):1. doi: 10.1007/s11934-015-0563-1.

Kim A, Shin DM, Choo MS.

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disease characterized by pelvic pain, usually with urinary frequency. These symptoms make patients suffer from a poor quality of life. However, there is still a lack of consensus on the pathophysiology and curable treatment of IC/BPS. We have reviewed several candidates for the pathophysiology of this disease and also treatments that have been used. Although several oral medications, bladder instillation therapies, fulguration for Hunner's lesion, and hydrodistention have been tried as IC/BPS treatments, their outcomes have not been satisfactory. As the application of stem cell therapy is expanding into the urologic field, innovative strategies have been tested with animal models of IC/BPS and have shown promising therapeutic effects for reversing the symptoms of this disorder. Although several concerns about stem cell sources and their safety should be addressed before initiating human clinical trials, we introduce stem cell therapy as a valuable future treatment approach for IC/BPS.

 
Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials.


Med Hypotheses. 2014 Jun;82(6):670-3. doi: 10.1016/j.mehy.2014.02.027. Epub 2014 Mar 4.

Adamowicz J1, Pokrywczyńska M2, Drewa T3.

 
Abstract
 

The treatment of Interstinal Cystitisis (IC) is still challenge for urologist. Available therapies do not result in long-term control of symptoms and do not provide pain relive to patients. Unique abilities of mesenchymal stem cells (MSC) could be used to develop new treatment approaches for Interstitial Cystitis. Conditioned Medium (CM) derived from MSC culture is rich in plenty of growth factors, cytokines and trophic agents which were widely reported to enhance regeneration of urinary bladder in different conditions. This ready mixture of growth factors could be used to develop intravesical therapy for patients with IC. MSC-CM has anti-apoptotic, anti-inflammatory, supportive, angiogenic, immunosuppressive and immunomodulative properties and seems to be ideal substance to prevent IC recurrence and to create favorable environment for regeneration of damaged bladder wall.

 
Stem cells for urinary tract regeneration.


Cent European J Urol. 2012;65(1):7-10. doi: 10.5173/ceju.2012.01.art2. Epub 2012 Mar 19.

Bajek A, Drewa T, Joachimiak R, Marszałek A, Gagat M, Grzanka A.

Abstract
 

Regeneration of the urinary bladder is a complicated task, due to organ dimensions and diseases (cancer, interstitial cystitis) when autologous bladder cells cannot be used. Cancer is the most frequent indication for bladder removal (cystectomy). Stem cells can be used with the guarantee of the sufficient cell number for the in vitro construction of the urinary bladder wall. Tissue engineering techniques hold great promise for regeneration of dysfunctional urinary sphincter. Denervation following surgical procedures or injuries results in weakness of the urethral sphincter and stress urinary incontinence. Injectable therapies and the potential of stem cells for sphincter restoration was presented in this review. The aim of this review was to present possibilities of urinary bladder regeneration with the use of stem cells and tissue engineering techniques.

 

 
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