Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome

This study is a Phase I trial to determine the safety of autologous mononuclear cells (MNC)
derived from umbilical cord blood for intramyocardial delivery into the right ventricle
during a planned and non-emergent Stage II surgical palliation in subjects with HLHS. This is
the first critical step towards applying autologous MNC therapy as an add-on regenerative
intervention for congenital heart disease management. The choice of HLHS as the target
disease for regenerative therapies in congenital heart disease management is multi-factorial
and includes the following considerations: 1) Severity of of this incurable disease, 2)
palliative nature and burden of long-term outcomes with a single right ventricular system, 3)
three stages of planned surgical procedures that provide time points to adjunctively
intervene, and 4) prenatal diagnosis enabling planned collection of UCB. An emerging goal for
cardiac regeneration includes the application of cell-based technology to congenital heart
disease, which is a favorable substrate due to the lack of fibrotic scaring, and the presence
of a microenvironment that is expected to support ongoing cardiac proliferation and growth
for functional remuscularization. This Phase I safety study will determine the feasibility of
collection, processing, and delivery of autologous cells as used in adult cardiac
regenerative protocols in the setting of HLHS surgical management.

Inclusion Criteria

1. Individuals with autologous cord blood product that met all cell release criteria
(listed on the certificate of analysis from Mayo Clinic Human Cell Therapy Lab) as
follows:

1. No aerobic or anaerobic bacterial growth after 14 days

2. Greater than 70% cell viability pre-freeze

3. Total Nucleated Cells (TNC) concentration of 30-42 x 106 cells/mL (pre-freeze)

4. Minimum of one (1) vial of cells

5. Mononuclear cell percentage of greater than 50%

6. Endotoxin result of less than 16 Endotoxin Units (EU)/mL.

2. Mother's serology test results are negative for HIV, Hepatitis B, and Hepatitis C.

3. Individuals with HLHS having undergone Stage I surgical palliation and undergoing
planned Stage II palliative Glenn surgery.

4. Ages up to 18 months are eligible if written informed consent can be obtained from
both parents (unless one parent is not reasonably available) and/or legal guardians.

Exclusion Criteria

1. Child who's UCB does not meet the specified cell release criteria in Inclusion
Criterion #1.

2. History of dimethyl sulfoxide (DMSO) reaction for either the child or mother.

3. Parent(s)/child unwilling to participate.

4. Child with severe chronic diseases, extensive extra-cardiac syndromic features, or
history of cancer.

5. Child not completing all pre-procedure work-up within 10 days of the Stage II Glenn
surgery as listed in section 6 of this protocol AND lack of pre-procedure work-up
documented as a safety concern by a site investigator.

6. Child who's cells have been compromised after meeting cell release criteria (as
defined in Inclusion Criterion #1).

7. Child with the following complications of their congenital heart disease:

1. Any condition requiring urgent, or unplanned procedure within 15 days prior to
Stage II surgical repair

2. Severe pulmonary hypertension (reported in the medical record as >70% systemic
pressure)

3. Other clinical concerns as documented by a site investigator that would predict
(more likely to happen than not to happen) a risk of severe complications or very
poor outcome during or after Stage II surgical repair.