For the investigational use of Adipose Derived
Stem Cells (ADSC's) for clinical research and deployment.
150 Avenida Cabrillo Suite A
San Clemente, CA 92672
Part of the
Post Prostatectomy Incontinence Protocol
In America alone, more than three million men are affected by loss of bladder control, a medical condition known as urinary incontinence. This problem has a great impact on health and quality of life for those who suffer with it. Male urinary incontinence is usually caused by a damaged sphincter, the circular muscle that controls the flow of urine out of the bladder. It often happens as the unavoidable result of prostate cancer surgery. When the sphincter is damaged, the man cannot squeeze or close off the urethra and leakage occurs especially with straining or exercise. Cell Surgical Network (affiliate) is using Stromal Vascular Fraction with
adipose derived adult mesenchymal stem cells to treat post prostatectomy incontinence.
The SVF and a small amount of condensed fat matrix is injected with a telescope directly into a deficient sphincter under local anesthetic. Based on experience from Nagoya University, Japan where Stromal Vascular Fraction has been used successfully for male incontinence, we believe that the external sphincter may be regenerated to some extent to provide bladder control. can provide access to the same technology through our investigatory protocol. (THIS PROCEDURE WOULD BE PERFORMED IN OUR RANCHO MIRAGE LOCATION)
polycystic kidney disease
Polycystic kidney disease (PKD), is one of the most common life threatening, inherited diseases in humans, affecting more than 1 in 500 individuals. Patients with the disease experience an abnormal proliferation of kidney cells that ultimately results in cysts and a decline in organ function leading to kidney failure. PKD comes in two forms. Autosomal dominant polycystic kidney disease (ADPKD) develops in adulthood and is quite common, while autosomal recessive polycystic kidney disease (ARPKD) is rare but frequently fatal. ADPKD is caused by mutations in either of two proteins, polycystin-1 and polycystin-2, while ARPKD is caused by mutations in a protein called fibrocystin. There is no cure or widely adopted clinical therapy for either form of the disease.
The mechanisms that cause cysts to form have long been poorly understood. Recently, a team of scientists from the HSCI Kidney Disease Program at Brigham and Women’s Hospital were able to reprogram the skin cells from five PKD patients—three with ADPKD and two with ARPKD—into induced pluripotent stem cells, which can give rise to many different cell types, and then differentiate them into other cell types. Adipose-derived stem cell therapy is now being studied as a potential therapy to repair kidney cells and/or delay further deterioration in kidney function.
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. Recent research indicates IC may be related to systemic neurosensitization and neuroinflammation that occurs within the bladder and also some other organ systems. 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.
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. 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 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.
We know that patients with IC demonstrate abnormal cell signaling and cytokine release. 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.
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 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. (THIS PROCEDURE WOULD BE PERFORMED IN OUR RANCHO MIRAGE LOCATION)
Peyronies Disease “PD” has been described by experts as a physically and psychologically devastating problem manifested by a fibrous inelastic scar of the fibrous chambers of the penis known as the tunica albuginea. The scarring (known as “peyronies plaques”) can cause pain, bending, narrowing, hinging and shortening of the penis in the erect state. Recent demographic studies have shown that up to 9% of men have this problem and it seems to be even more prevalent after radical prostatectomy surgery. More than half of the cases worsen over time and only 13% resolve spontaneously. Peyronies is also closely associated with erectile dysfunction. There is no known non-surgical cure for PD and surgery can often result in more scarring, shortening or loss of sensation and adequate erectile function. Cases that involve calcification seem to do the worst with non-surgical treatment. Non-surgical
therapies include: Vitamin E, Potaba, colchicine, tamoxifen, carnitine, and Omega-3 fatty acids. Unfortunately, formal studies have shown no benefit of any of these over placebo. Verapamil cream is often used by clinicians but there are no controlled trials proving that the verapamil penetrates into the tunica albuginea. There have been eight studies on intralesional injection of verapamil showing some positive effects in decreasing curvature and deformity improved in 30% to 60% of patients. The usual treatment is 10 mg injected every two weeks a total of twelve times. Injection of interferon alpha 2b has shown very mixed results. There is an ongoing FDA study of a drug (phase 3) called Xiaflex which is made from bacterial collagenase. Early results may be promising with curvature reduction 20% higher than with placebo. There are some ongoing European studies of a penile traction device that stretches the penis and early results seem to indicate a benefit but it involves a rigorous daily application of a device to the penis. There is evidence that stem cells will actively seek out and attempt to repair a Dupytren’s contracture which is nearly identical to PD but occurs in the hand. Stem cells may be highly effective in inflammatory scarring conditions occurring in other parts of the body. We have developed a protocol for intralesional injection of autologous adipose derived stromal vascular fraction (rich in mesenchymal stem cells and growth factors) directly into Peyronies plaques as a non-surgical option for patients who have not responded to other conservative measures but wish to avoid surgery. Some patients will also be eligible to receive low intensity shock wave therapy in conjunction with SVF deployment in an effort to activate the stem cells to induce revascularization and healing. (THIS PROCEDURE WOULD BE PERFORMED IN OUR RANCHO MIRAGE LOCATION)
Erectile Dysfunction (ED) is defined as the inability to achieve or sustain an erection suitable for sexual intercourse. ED affects up to one third of men of men throughout their lives and has a substantial negative impact on intimate relationships, quality of life and self-esteem. Causes are multifactorial but can be related to loss of testosterone, surgical damage to the penile nerves, medications, or other medical illnesses. The most common cause of ED is “vasculopathy”, which is damage to the delicate blood vessels in the penis. This vasculopathy is often associated with age but strongly related to atherosclerosis, diabetes, hypertension, high cholesterol and cerebrovascular and peripheral vascular disease. Vasculopathy is also very prominent in patients with Peyronies disease and penile scarring. Men with ED are also at significantly increased risk of coronary artery disease. Therefore, when men have ED,
screening for cardiovascular risk factors should be considered because symptoms of ED present as much as three years earlier than other symptoms of coronary artery disease such as chest pain.
The current treatment of ED centers around the use of Phosphodiesterase type 5 inhibitors such as Viagra, Cialis, or Levitra. Intraurethral pellets and intracavernosal (penile injectable agents) are also available if oral medications fail. Various mechanical external vacuum pump devices are helpful also in patients who are comfortable with assisted devices. Penile revascularization surgery has mostly fallen out of favor due to poor outcomes in most patients. At this time, the only treatment available to patients who have not succeeded with any of the above are surgically implanted hydraulic penile prostheses. These surgeries are somewhat invasive but often effective. Adipose derived stem cells have shown extraordinary promise in revascularizing cardiac tissue, ischemic limbs and other organs suffering damage from poor blood flow by regenerating small blood vessels as well as smooth muscle and nerves. We have evidence that adipose derived stem cells stimulate endothelial (small blood vessel lining) growth and improve penile blood flow in animal models. Early attempts have been made in human patients to improve erectile function using adult mesenchymal stem cells however results have been inconsistent. There is some evidence that results will be optimized if the transplanted stem cells are “activated.” The process of stem cell activation is usually a natural phenomenon induced by inflammatory and ischemic events. However, chronic micro-vasculopathy may require tissue micro-trauma to induce cellular healing and angiogenesis. Controlled tissue micro-trauma can be induced using low intensity shock wave treatment of the penis has been used successfully for years for penile pain associated with Peyronies disease. In 2012, a publication in the Journal of Urology (See Citation) provided evidence that shock wave technology alone can significantly improve erectile function in comparison to placebo treatment. (THIS PROCEDURE WOULD BE PERFORMED IN OUR RANCHO MIRAGE LOCATION)