Cellular & Biocellular Regenerative Therapy in Musculoskeletal Pain, Dysfunction,Degenerative or Inflammatory Disease

Musculoskeletal disorders and degeneration represent injuries or pain in the body's joint
ligaments, tendons, muscles, nerves, and skeletal elements that support extremities, spine
and related tissues. Direct injuries and aging contribute to breakdown and inflammation of
these tissues, leading to debilitation and loss of function in these areas. This has major
impact on quality of life, occupational/recreation limitations, and psychosocial
implications.

Many therapies have been employed including medications, physical therapy, occupational
therapy, and a variety of surgical interventions each of which have distinct limitations,
often covering the issues versus providing actual healing and return to function. Many
reports are now available utilizing self-healing options which include use of stem/stromal
cells (either from adipose or marrow) using targeted placement of cells, matrix and platelet
concentrates. This is termed Biocellular therapy, and typically is optimized by use of
ultrasound guidance. It is proposed that use of cellular isolates derived from the largest
deposit of these cells (adipose greater than marrow), may use in conjunction with targeted
placement or as a stand alone methodology of parenteral use.

This study is designed as a interventional means to examine the safety and efficacy of the
use of cellular stromal vascular fraction (cSVF) in musculoskeletal pain, dysfunction
degeneration or inflammatory disorders. The important cellular components represent, not the
adipocyte, but the heterogeneous cell group associated with the peri-vasculature. The group
does include certain cells referred to as "stem" or "stromal" cells, and are considered key
elements of cellular and biocellular treatments. The carrier microvascular tissue, adipose,
has been shown to not participate in wound healing or cellular replacement per se. It is well
established that those perivascular (adventitial) cell types are found in essentially all
tissues of the body, but in highest numbers in the easily accessed depots with the subdermal
fat. It is proposed that areas of these groups are responded to as a result of "signaling" to
permit a chemotactic request for needed growth factors and cytokines which effectively
contribute to the healing capability at failing or damaged sites. This Trial will investigate
the safety/efficacy of either combining specific targeting (ultrasound) with and/or without
systemic parenteral route introduction.

This study includes closed syringe, disposable microcannula harvesting of subdermal fat
tissues for obtaining the native perivascular stromal elements (extracellular matrix (ECM)
and periadventitial cells shown to be multipotent (in potentials), incubation, digestion and
isolation of cSVF. This isolated and concentration of stem/stromal cellular pellet (without
actual extracellular matrix or stromal scaffolding elements) is then suspended in 500 cc
sterile Normal Saline (NS) and deployed via peripheral intravenous route. Evaluations of
safety issues are measured at intervals (both severe and non-severe categories) and by
ultrasound and imaging studies.

Biocellular treatments are defined as use of tissue stromal vascular fraction (tSVF) obtained
within adipose tissue complex (ATC), combined with high density platelet rich plasma (HD PRP)
concentrated from standard blood draw. Concentration in FDA approved platelet concentrate
devices to achieve levels of >4 times patient's own measured baseline levels. Such
concentrates have been shown to provide important growth factors and cytokines (signal
proteins) naturally involved in wound healing and repair functions. A form of Cell-Enriched
Biocellular Therapy (CEBT) is available as a component of this study, in which the tSVF + HD
PRP can be enhanced in cellular numbers via the process of isolating and concentrating cSVF
discussed above. Many small case series and case reports have been published in the peer
reviewed medical literature which suggest that these interventions are both safe and
effective at relieving musculoskeletal disorders included in the study.

This study in intended to provide evidence of a non-drug safety and efficacy using both of
these interventions. Evaluation and tracking of adverse events or severe adverse events (SAE)
will be tracked according to intervals described. Examination of the optimal numbers of
cells, viability of such cells, and evaluation of the efficacy will be statistically studied
reported relative outcomes.

Inclusion Criteria:

- Patients with documented inflammatory, autoimmune (rheumatoid arthritis (RA),
degeneration of musculoskeletal system

- No systemic disorders which, in the opinion of the principal investigators or
provider, would disqualify from being safely able to undergo needed procedures

- Able to provide informed consent

- Patient having adequate donor adipose (fat) tissue

- Patient mature enough to tolerate the needed procedures

Exclusion Criteria:

- Systemic or psychological impairment which would preclude patient tolerance and
understanding of procedures and follow up

- Patients with known active cancer and chemotherapy or radiation therapy

- Patients with ongoing active infections

- High dose steroid users or use of injections of corticoid steroids within a six month
timeframe

- Opiate addition or in treatment program for withdrawal

- History of severe traumatic brain injuries

- If, in the opinion of providers, the patient will not be able to fully cooperate or
complete the study and its follow up