Use of Adipose-Derived Stem/Stromal Cells in Concussion and Traumatic Brain Injuries

Concussion Syndrome (CS) and TBI are common injuries producing temporary and long-term damage
to impact brain function. Symptoms are sometimes transient, sometimes long-term depending on
severity and/or repetitive damage. Signs varying from recurrent headaches, mental fog,
emotional changes to physical signs of loss of consciousness, amnesia to behavioral change
(irritability, loss of concentration ability, etc.), cognitive impairment (slow reaction
times, memory loss), and recurring sleep disturbances.

Common causes include sports injuries, automobile accidents, falls, blunt trauma to head, and
explosive/blast injuries from production of acceleration injuries

Treatment often involves monitoring, physical rest, limiting cognitive activities (such as
computing, video games, texting, and studying). Most often a single episode usually resolve
or improve (particularly in recurring headaches) within 3-4 weeks. It is estimated that
>6/1000 occurrence rate apply. Repetitive injuries seem to make the person more susceptible
to additional damage, particularly with injury precedes resolution of an earlier damage.
There appears also to make persons to require a lesser impact to produce the same degree of
severity. It is becoming more recognized that repeated concussions increase the risks in
later life for dementia, Parkinson's and severe depressions.

Most serious signs to evaluate are loss of consciousness, seizures, worsening headache,
diplopia/pupil changes, loss of recognition, vomiting, focal neurological problems, and
change of personality.

There is no consensus definition of concussion or TBI. Most concussions are considered in the
mild TBI (mTBI) group, and are rarely demonstrate structural brain damage when in the acute
to subacute state. Late brain MRI changes are difficult to clearly point to or identify the
specific areas of presumed damage.

This study is intended to examine safety and efficacy of parenteral introduction of AD-cSVF
in cases of CS and TBI, and categorically examine the outcomes according to the elapsed time
from original concussive event. No delineation of those having recurrent damage and injuries
are made within this study.

Inclusion Criteria:

- Documented history of mTBI or TBI with Correlated MRI or CT

- At least 1 month post mTBI and TBI

- Able and Willing to participate in CT or MRI pre-study and at 3 year, 5 year interval

- Able to provide informed consent to undergo the study

- Depression, Cognitive Disability, Attention Disorders, Headaches or other persistent
changes which followed a traumatic brain event (TBI)

- Impaired social or occupational functioning following mTBI or TBI

- History of repetitive events for mTBI and TBI

Exclusion Criteria:

- Documented history of neuro-degenerative illness, seizures, mental illness, or severe
medical conditions preceding mTBI or TBI

- Malignances, Bleeding Disorders, Pregnancy or Lactation

- Tumors of Central Nervous System (CNS)

- Lack of adequate donor tissue volume as determined by the primary investigator at
their discretion

- Any pre-existing medical condition which, in view of the primary investigator and
patient's primary care physician, would prevent participation in study