Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)

Primary osteoarthritis is a debilitating disease characterized by extensive damage to the
joints and excruciating pain leading to loss of activity and depression. Despite advances in
diagnosis and relatively efficient control of nociception, to date, the quest for the
development of a disease modifying osteoarthritis drug has proven unsuccessful. The potential
of mesenchymal stem cells to inhibit inflammation while promoting healing makes them amenable
for the treatment of various ailments ranging from cancer to genetic diseases. In orthopedic
practice, autologous stem cell injections are performed to alleviate the pain associated with
osteoarthritis. A serious gap in knowledge remains whether the currently used cellular
treatments are beneficial in the long term and if one cell therapy outperforms another.

The most popular form of Autologous Mesenchymal Stem Cells (MSC's) therapy has been through
the use of Autologous Bone Marrow Concentrate (BMAC). The rationale is that when a sample of
Bone Marrow Aspirate (BMA) is collected and the components that are not beneficial to the
joint are filtered out (i.e. red blood cells, neutrophils, etc.) the remaining concentrate
(MSC's, platelets, interleukins, etc) can have a "healing" effect on the environment in which
it is injected. However it is still unknown as to how effective BMAC is for treating
orthopedic conditions compared to other MSC procedures and the most important components of
the BMAC mixture that could aid patients suffering from osteoarthritis.

Adipose tissue has been found to have a large amount of mesenchymal stem cells versus that in
bone marrow. These cells are currently being used in a variety of clinical research studies
within the regenerative medicine field. Through a tissue process which includes washing and
centrifuging, the cellular components can be extracted as a cell pellet, which is also known
as Stromal Vascular Fraction (SVF). Adipose derived SVF is obtained via liposuction, or the
removal of adipose tissue via a suction method.

Although the use of various stem cell preparations for knee osteoarthritis has become
increasingly prevalent, well-designed studies with conclusive proof of comparative
effectiveness and identification of the optimal cell source and "dose" have not been
performed. This study is the first randomized study comparing three types of cellular
treatments to corticosteroids. The main objective of the study is to identify a superior
source of stem cells for the treatment of osteoarthritis and validate its advantages over
corticosteroid injections as the traditional gold standard treatment.

Inclusion Criteria:

- Age >40 but <70 years old

- Males and females

- Recent knee radiograph of the targeted knee (standing AP lateral and sunrise view)

- Diagnosis of OA in the targeted knee (radiographic evidence of OA in the medial and/or
lateral tibiofemoral compartment, which would include one or more osteophytes on a
standard radiograph taken within 3 months)

- Continued OA pain in the targeted knee despite conservative measures (per treating
provider's discretion)

- Average daily VAS ≥3

- Kellgren-Lawrence system of Grade II, III, or IV

- Subjects may have concomitant patellofemoral but they must have stage II or higher
generalized knee OA

- Females of childbearing potential only, must have a negative pregnancy test done ≤ 7
days prior to enrollment in the study

- Women and men of child-producing potential must agree to use acceptable contraception
methods for the duration of the trial such as birth control pills or condoms with
spermicide

Exclusion Criteria:

- Clinically apparent tense effusion of the targeted knee

- Significant valgus/varus deformities (+/- 5 degrees)

- Viscosupplementation within 6 months in the targeted knee

- Other biologic injection (PRP or stem cell) within 1 year in the targeted knee

- Surgery in the targeted knee within the past 6 months (either open or scope)

- Systemic or intra-articular injection of corticosteroids in any joint within 3 months
before screening

- Daily opioid use for the past three months

- History of malignancy in the previous 5 years prior to study entry, with the exception
of in-situ cancers treated only by local excision with curative intent

- History of, or ongoing, autoimmune disorder that requires treatment with an
immunosuppressive medication

- Active, suspected, or prior infection to the joint in the targeted knee

- Part of a vulnerable population per OHRP definition (pregnant women and breast-feeding
women, cognitively impaired, prisoners, etc.)

- Use of NSAIDS within 1 week of the procedure

- Unwilling to discontinue use of NSAIDS for 5 calendar days after procedure

- History of bleeding disorders or inflammatory joint disease

- Inability to hold anti-platelet therapy according to treating provider prior to
procedure

- If deemed medically inappropriate or noncompliant by the treating investigator

- Uncontrolled diabetes

- Subject has an active workers' compensation case in progress

- Subject with insufficient amount of subcutaneous tissue to allow recovery of a minimum
of 100 mL of lipoaspirate

- Hemoglobin less than 10g/dL at the time of screening

- Leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets
<100,000/μL at the time of screening

- Diagnosis of liver disease as defined by alanine aminotransferase (ALT) >3x the upper
limit of age-determined normal (ULN) or total bilirubin > 1.5x ULN

- Subjects who have had greater than 3 corticosteroid injections in the targeted knee in
the 12 months prior to screening and at the physician's discretion

- Subjects with a known diagnosis of osteoporosis

- Subjects with anticipated use of systemic corticosteroids during the study period for
treatment of a chronic medical condition