Cell Therapy for Craniofacial Bone Defects

Up to 20 (twenty) subjects who have alveolar defects secondary to clefts (n=10) or trauma
(n=10), will be selected to participate in this study. Among the 20 patients, a total of up
to 60 defect sites will be evaluated for bone regeneration following therapy, with each
subject being evaluated in from one to four sites. Once enrolled, subjects from each of the
two groups (cleft or trauma) will be randomly assigned to receive one of two possible
treatments, traditional autogenous bone grafting or cell therapy (ixmyelocel-T)

Inclusion Criteria:

- Age range: 18 to 60 yrs

- Gender: Male and female

- Patients must be able and willing to follow study procedures and instructions.

- Patients must have read, understood and signed an informed consent for

- Missing tooth criteria:

- Patients missing at least one maxillary lateral incisor secondary to cleft lip
and/or palate:

- with compromised bone support for installation of dental implant(s) ( > 3
mm deficiency in horizontal and/or vertical bone height)

- with adequate interdental arch space for dental implant restorations

- with bony continuity between cleft segments

- with adequate interproximal space (between adjacent teeth) for dental
implant installation

- Patients missing multiple (1-4 teeth) teeth secondary to trauma:

- in maxillary or mandibular anterior segments (second premolar to second
premolar)

- with compromised bone support for installation of dental implant(s) ( > 3
mm deficiency in horizontal and/or vertical bone height)

- with adequate interdental arch space for dental implant restorations

Exclusion Criteria:

- Allergies or hypersensitivities to study related medications: dexamethasone,
chlorhexidine, ibuprofen. For patients allergic to amoxicillin a comparable
substitute antibiotic will be used.

- Hematologic disorders/ blood dyscrasias. Patients will have blood drawn for a
complete blood count (CBC) test. Current University of Michigan Health System normal
lab values are as follows: white blood count (WBC: 4.0-10.0 x103/cmm), red blood
count (RBC: male 4.50-5.90 x103/cmm; female 3.90-5.30x103/cmm), hemoglobin (HgB: male
13-17.3gm/dl; female 12-16gm/dl), Hct (male 39-50.2%; female 35-48%), mean
corpuscular volume (MCV: 80-100fl), mean corpuscular hemoglobin (MCH: 25-35 pg), mean
corpuscular hemoglobin concentration (MCHC: 30-37%), red cell distribution width
(RDW: 11.5-15.5%), Plt (150-450x103/cmm).

- Active infectious disease

- Liver or kidney dysfunction/failure- Patients will have blood drawn for serum
laboratory tests, including creatinine, blood urea nitrogen, aspartate
aminotransferase test (AST), alanine aminotransferase test (ALT), and bilirubin.

- All of these must be within normal limits for a patient to be included in the study.

- Current University of Michigan Health System normal lab values are as follows:
*Creatinine (male 0.7-1.3 mg/dl

- female 0.5-1.0 mg/dl)

- blood urea nitrogen (BUN: 8-20 mg/dl)

- AST (8-30 IU/L)

- ALT (7-35 IU/L)

- Bilirubin (0.2-1.2 mg/dl).

- Laboratory values that will define normal renal and hepatic function, as well as
criteria for exclusion of metabolic bone disease are consistent with those
established by the University of Michigan Health System (UMHS).

- Normal clinical values will be used to help assure the health of all subjects in this
trial.

- Potential subjects whose laboratory values fall outside the UMHS normal ranges will
be required to have medical clearance from their primary care provider prior to
participation.

- Endocrine disorders/dysfunctions (i.e uncontrolled Type I or II diabetes,
glycosylated hemoglobin [HA1C > 7%})

- Cancer - The explicit definition of cancer used to exclude patients is consistent
with that described by the National Cancer Institute (NCI), National Institutes of
Health. According to NCI, cancer is any disease in which abnormal cells divide
without control and invade nearby tissues (invasive disease). These include
carcinomas, sarcomas, leukemias, and lymphomas. Any patient with a history of these
invasive diseases will be excluded from the study.

- Patients who currently use bisphosphonates or have a history of bisphosphonate use
will be excluded from the trial.

- HIV+

- Metabolic Bone Diseases- Patients with metabolic bone diseases such as Paget's
disease, hypercalcemia, moderate to severe vitamin D3 abnormalities or any other
metabolic bone disease including osteoporosis and osteoporotic fractures will be
excluded. The following scale will be used to determine osteoporosis in patients who
have had a bone mass density (BMD determination: Normal = T score at or above -1.0
standard deviation [SD]); Osteopenia = T score between -1.0 and -2.5 SD; Osteoporosis
= T score at or below -2.5 SD.

- Pregnant women- Female patients who are of childbearing potential are excluded except
those who are using hormonal or barrier methods of birth control (oral or parenteral
contraceptives, diaphragm plus spermicide, or condoms). Pregnancy status will be
determined with a urine test and patients who are pregnant, as determined by a
positive test, will be excluded from the study

- Patients with congenital or metabolic bone disorders

- Subjects with co-morbid conditions that would affect the study outcome or
interpretation of study results will be excluded

- Subjects on significant concomitant drug therapy for systemic conditions (i.e.
cardiovascular disease, renal dysfunction) will not be included in the study.
Occasional short term use (7-14 days) of analgesics or common cold medication is
permitted. Such use of these medications will be reviewed and recorded by the
Investigator.