Hypoxia-inducible Factor-1 (HIF-1) Regulated Circulating Angiogenic Cells (CACs) Recruitment in Burn Wound Healing

Burn injuries represent a major public health problem, requiring medical attention for more
than one million Americans annually. Despite therapeutic advances, non-healing burn wounds
and excessive scarring still result in significant long term physical and psychosocial
morbidity. In this study we propose to perform clinical and research to study the role of
circulating angiogenic cells (CAC) in promoting burn wound healing.

CAC's have been shown to contribute to vascularization and tissue repair in a number of
animal models of tissue injury ischemia and mobilization of CACs into the peripheral blood
has been demonstrated in burn wound patients.

We hypothesize that primary healing of burn wounds is dependent on repair of damaged
vasculature, and that bone marrow derived stem cells, circulating angiogenic cells (CAC),
play a critical role in the healing process. Furthermore we propose that the transcription
factor Hypoxia Inducible Factor 1 alpha (HIF 1 alpha) through production of peptide products
of its downstream target genes directs the "homing" of CAC's to the wound where they
participate in healing events. The first aim of this study is to correlate mobilization of
CAC's into the blood stream with the success of burn wound healing.

CAC's have been shown to contribute to vascularization and tissue repair in a number of
studies. The relationship between mobilization of CAC's and burn wound healing has not been
examined. In addition to surveying CAC numbers in the peripheral blood, we will assay levels
of the putative mediators of CAC mobilization: Vascular Endothelial Growth Factor (VEGF),
Placenta Growth Factor (PLGF), and Stromal Cell-Derived Factor (SDF-1). We hypothesize that
individuals who are able to mount a large and sustained mobilization of CAC's into the
peripheral blood from the bone marrow, will be more likely to heal the injured vasculature
and go on to primary healing. Individuals with an inadequate mobilization of CAC's will fail
to repair the damaged vasculature in the wound and proceed to necrosis and "conversion" to
third degree, necrotic burn wounds.

Inclusion Criteria:

Recruitment of patients at the Johns Hopkins Regional Burn Center for study will be based
upon the following clinical criteria:

- Second degree scald burn of 10 cm2

- Age between 14 to 75 years

- Burn area equal or less than 95% of Burn Surface Area (BSA)

- Body temperature between 98.5 and 101 degree F

- Informed consent for enrolment into study

- Spanish speaking patients will be included when we have a Spanish consent form
available.

Exclusion Criteria:

- First and third degree burn wounds

- Hemodynamic instability (SBP below 100, Heart Rate (HR) over 100, urine output less
than 30 ml/hour

- Area of burn over 20% of BSA

- Hypothermia T<98.5 or Hyperthermia T>101 degree F

- Urine output less than 30 ml/hour

- Serum albumin less than 3 mg/ml.

- Subjects weighing less than 50 kg.