From ones’ own fat, adipose-derived stem and regenerative cells (ADRCs) are a diverse population of cells that, through multiple activities, have the potential to help improve the urinary symptoms and pelvic pain that undermine the quality of life for men living with symptoms of an enlarged prostate, erectile dysfunction (ED) and Peyronie’s disease.

Chronic, low level systemic inflammation (inflammaging) is correlated with the major age-related degenerative diseases.^[1] Chronic inflammation can affect any and all parts of the body. In fact, diseases with a local inflammatory causation and/or systemic inflammation involvement often lead to other serious chronic conditions. People with Metabolic Syndrome (which involves cardiovascular, stroke, diabetes Type 2 and other risk factors including benign prostatic hyperplasia [BPH, or enlarged prostate] and ED) are well recognized to have their bodies in a proinflammatory state.^[2] A high concentration of tumor necrosis factor alpha (TNF-alpha)—proteins which promote inflammation—has also been associated with Metabolic Syndrome.

The Spiral of Degeneration

An inflammatory response can be triggered by a trauma, infection, environmental toxins, obesity, lifestyle choices (e.g. smoking), hereditary factors or a combination of those bad actors. The cells in the immune system (immune cells) are there to guard the body. When they sense the enemy, they send out troops of signaling molecules called proinflammatory “cytokines” to fight the bad actors off. This initial inflammation (acute) is essential for repairing the body, and is usually short-lived, disappearing once the healing process has taken place. When this process goes out of control, it is called an inflammatory-immune response, triggering chronic inflammation.

It is chronic inflammation that begins a vicious degenerative process. An overactive inflammatory-immune response is tantamount to having a backseat driver who is chronically overreacting while “helping” you drive your car. This then leads to reduced blood flow (ischemia). Without good circulation, cells die off, scars form, tissues and organs degenerate. We call this the Spiral of Degeneration.

The Spiral is a very relevant framework with which to understand the detrimental process and effects of BPH and other issues affecting men’s health. High blood pressure, diabetes, heart disease, chronic kidney disease and nerve injury from prostate surgery and radiation are some of the physical conditions that can cause ED. For conventional ED medications to work, the nervous system pathways must be intact, which is often not the case.

In addition to underlying inflammatory-immune response, age-related impairment of blood supply to the lower urinary tract is important in the development of BPH and ED. Vascular damage may cause chronic ischemia and thus be a contributing factor in the disease progression of BPH and ED.^{[3] [4]} As explained previously, the ischemia leads to cell death and fibrosis, which can then result in ED, bladder dysfunction and Peyronie’s disease.

Process of Repair

ADRCs are akin to having your own, personalized fire department. They wait quietly for a sign of trouble—inflammation—and then home to that site to do their jobs.

Through cell-to-cell communication known as paracrine signaling, ADRCs mobilize nearby cells to work more efficiently. In other words, ADRCs recruit repairmen at the site (resident stem cells) to get back on the job and do their part.

As an extended team, they first decrease inflammation and the overactive immune responses. Once the backseat driving diminishes they increase circulation with new blood vessel growth, prevent further cell death (apoptosis), decrease scar size and regenerate healthy tissue and nerves. This is how the body naturally heals, sometimes it just needs reinforcements.

We call this the Process of Repair. It involves the multiple mechanisms of action that are needed to bring the systemic inflammation and immune system back to balance. Blood flow is restored, further programed cell death prevented and scar has been seen to be reversed.

Animal studies have shown that stem cell therapy for erectile dysfunction can regenerate nerves, muscle, and vascular tissue.^{[5] [6]} The safety of treatment with ones’ own stem cells (autologous) has been established by Phase 1 studies.^[7] Stem cell recipients have shown improvements in ED.^[8]

Along with ED, urinary incontinence is a common consequence of treatment for prostate cancer. After establishing effectiveness in animal models, a study of local injection of ADRCs demonstrated safety and effectiveness in men that had urinary dysfunction after pelvic radiation.^[9]

In Peyronie’s disease, penile curvature results from fibrous, scar-like plaques forming in the soft tissues. Scar resolution is a well-documented effect of stem cells in animal models of the condition.^{[10] [11]} However the natural healing substances secreted by the stem cells and the cells’ biochemical messaging effect on neighboring cells also play an important role.^[12] Human studies have demonstrated that stem cell therapy can decrease and eliminate plaques in Peyronie’s disease.^[13] Many researchers consider treatment of Peyronie’s with ADRCs to be a feasible, safe and potentially effective therapy.^[14]

AMBROSE Cell Therapy for Men’s Health

In summary, the Spiral of Degeneration is involved in the progression of BPH, ED and Peyronie’s disease symptoms. However, men can now potentially benefit from AMBROSE Cell Therapy using ADRCs and the process of repair they initiate.

Of critical importance, because these cells come from you and have the innate purpose to repair, they have a remarkable safety profile—particularly as compared to drugs, surgery and devices.

AMBROSE utilizes two biologic preparations in our protocols:

• ADRCs liberated from the tissue by centrifuge with an enzyme for IV infusion.
• ADRCs resident in clean, micronized adipose tissue (tADRCs) enriched with; platelet rich plasma (PRP) for ultrasound guided, direct injections into the perineum, the area between the anus and the scrotum. This provides a safe delivery path to the prostate. ^{[15] [16]}

AMBROSE Cell Therapy represents a minimally invasive option for men struggling with symptoms of enlarged prostate, ED and Peyronie’s. Please contact us for more information about treatment, candidacy and how to become a patient.

[1] T.K Howcroft et al The role of inflammation in age‐related disease AGING, January 2013, Vol. 5 No 1

[2] JH Fowke, T Koyama, O Fadare, PE Clark Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms. PLoS ONE 11(6): e0156918 (2016)

[3] A Berger et al Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction BJU International 96, 107 3 – 107 8 (2005)

[4] A.P. Berger et al Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease? BJU International, 98: 587–590. (2007)

[5] Gu X1, Shi H, Matz E, Zhong L, Long T, Clouse C, Li W, Chen D, Chung H, Murphy S, Yoo J, Lin G, Lue T, Atala A, Jackson J, Zhang Y. Long-term therapeutic effect of cell therapy on improvement in erectile function in a rat model with pelvic neurovascular injury. BJU Int. 2018 Nov 30.

[6] Al Demour S, Jafar H, Adwan S, et al. : Safety and Potential Therapeutic Effect of Two Intracavernous Autologous Bone Marrow Derived Mesenchymal Stem Cells injections in Diabetic Patients with Erectile Dysfunction: An Open Label Phase I Clinical Trial. Urol Int. 2018;101(3):358–65

[7] Protogerou V, Michalopoulos E, Mallis P, Gontika I, Dimou Z, Liakouras C, Stavropoulos-Giokas C, Kostakopoulos N, Chrisofos M, Deliveliotis C. Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study. Bioengineering (Basel). 2019 Mar 5;6(1). pii: E21

[8] European Association of Urology. “Stem cells shown to restore erection capability in men with erectile dysfunction.” ScienceDaily, 27 March 2017.

[9] Choi JY, Kim TH, Yang JD, Suh JS, Kwon TG. Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study. Yonsei Med J. 2016 Sep;57(5):1152-8

[10] Castiglione F, Hedlund P, Van der Aa F, et al. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie’s disease. Eur Urol 2013; 63: 551–560

[11] Gokce A, Abd Elmageed ZY, Lasker GF, et al. Intratunical injection of genetically modified adipose tissue-derived stem cells with human interferon α-2b for treatment of erectile dysfunction in a rat model of tunica albugineal fibrosis. J Sex Med 2015; 12: 1533–1544

[12 Lin CS, Lue TF. Adipose-derived stem cells: therapy through paracrine actions. In: Hayat MA, editor. , (ed.) Stem cells and cancer stem cells. Vol 4 New York, NY: Springer, 2012, pp.203–216

[13] Levy JA, Marchand M, Iorio L, et al. Effects of stem cell treatment in human patients with peyronie disease. J Am Osteopath Assoc 2015; 115: e8–e13

[14] Krzastek SC, Bopp J, Smith RP, Kovac JR. Recent advances in the understanding and management of erectile dysfunction. F1000Res. 2019;8:F1000 Faculty Rev-102. Published 2019 Jan 25. doi:10.12688/f1000research.16576.1

[15] V Cervelli, P Gentile, B De Angelis, et al Application of enhanced stromal vascular fraction and fat grafting mixed with PRP in post–traumatic lower extremity ulcers. StemCells 20116:103–11.

[16] M Tobita et al Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness Stem Cell Research & Therapy (2015) 6:215