Use of Autologous Adipose-Derived Stem/Stromal Cells (AD-cSVF) in Symptomatic Benign Prostate Hypertrophy

Benign prostate hypertrophy (BPH) and inflammation are common non-cancerous enlargement of
the prostate, which result in urinary interference and incomplete drainage of the bladder.
Compression of the urethra is common cause of such resistance of full draining, and may over
time result in progressive hypertrophy, instability, urgency, nocturia and weakness of the
bladder musculature.

Prostatic growth frequently begins in the 30s, and it is estimated that 50% of all males have
benign enlargement leading to 75% by age 80. BPH and low grade inflammation is one of the ten
most prominent and costly disorders in males over 50. BPH is often a progressive disease and
may lead to increased urinary stasis and increased risk of urinary tract infections.

Urinary tract symptoms are divided into issues of storage, voiding, and post-void symptoms
can be associated with bladder outlet obstruction (BOO). Storage symptoms include need to
urinate frequently, waking at night to urinate (nocturia), and incontinence (involuntary).
Voiding issues include urinary hesitancy, intermittency (start/stopping flow), leaking after
voiding and may include some pain (dysuria) associated with urination. Post-voiding symptoms
include abdominal pain, feeling of full bladder, acute urinary retention and frequency,
dysuria, hesitancy, etc.

Causation may be associated with age related changes in androgens (such as testosterone and
others), but do not seem to be the direct cause of the enlargement.

Androgens promote prostate cell proliferation, but relatively low levels of testosterone are
often found in patients with BPH.

Treatment often has been aimed at lifestyle change (exercise, decrease nighttime fluid
intake, moderating alcohol and caffeine, decrease certain anticholinergic medications. Use of
medication have some advantages, including alpha blocker and 5 alpha-reductase inhibitors,
and some broad spectrum antibiotics (like Ciprofloxacin) seem to help many of those with
increasing symptoms. Self catheterization and surgery are occasionally needed for patient
comfort and reduction of symptomatology.

Alternative remedies include herbal remedies (saw palmetto) and anecdotal effects in patients
receiving parenteral stem/stromal cell therapies for other clinical issues. Initially
commented that the patient reported improvement of symptoms, have led to this study to
determine if any long-interval therapy may be as effective as surgery or catheterization.

This study utilizes isolation of adipose-derived stem/stromal cellular stromal vascular
fraction (AD-cSVF) deployed as an IV suspension in sterile Normal Saline (500cc). Due to the
anti-inflammatory and immunomodulatory effects common to AD-cSVF are tested in relief of the
inflammatory elements and the concurrent hypertrophy in BPH. Early pilot use has suggested a
positive effect on these issues, and have relieved much of the incomplete voiding, pain,
nocturia, delay in starting/stopping urination, and increased urgency and frequency.

Lipoharvesting of Adipose-Derived tissue stromal vascular fraction (AD-tSVF) is now a common
closed access to subdermal adipose stromal/stem cell population consisting of both stem and
stromal cells, each of which are felt to contribute a wide variety of effects and potentials.
Closed, sterile isolation of the AD-cSVF is possible with advent of closed systems to
enzymatically release these cells from the actual matrix (scaffolding) within the adipose
tissue complex (ATC). This group of largely un-designated cell population is isolated and
concentrated via a standard gradient layer separation by centrifugation. This cellular
isolate is then suspended in an IV of 500 cc Normal Saline and reintroduced to the patient.

This study is examining the clinical safety and efficacy of this approach, as well as
tracking the duration of effects and establish a therapeutic interval.

Inclusion Criteria:

- Documented history BPH for at least 1 year

- AUA SI greater than or equal to score of 15

- Qmax < 15 ml/sec

- Severe nocturia

- Prostate Specific Antigen (PSA) > 4 ng/mL with documentation of non-malignancy

Exclusion Criteria:

- History of illness or conditions that may interfere with study or endanger subject

- Use of prescription medication that may interfere with study or endanger subject
within 30 days

- History of surgical procedures for BPH or documented prostate cancer

- Post-void residual urine volumes of > 350 cc

- PSA > 10 ng/mL

- Prostate cancer not ruled out by biopsy if PSA is consistently higher than 4 ng/mL