Tissue engineering of viable, autologous cardiovascular constructs with the potential
to grow, repair, and remodel represents a promising new concept for cardiac surgery,
especially for pediatric patients. Currently, vascular myofibroblast cells (VC) represent
an established cell source for cardiovascular tissue engineering. Cell isolation requires
the invasive harvesting of venous or arterial vessel segments before scaffold seeding,
a technique that may not be preferable, particularly in pediatric patients. In this
study, we investigated the feasibility of using umbilical cord cells (UCC) as an alternative
autologous cell source for cardiovascular tissue engineering.
Human UCC were isolated from umbilical cord segments and expanded in culture. The
cells were sequentially seeded on bioabsorbable copolymer patches (n = 5) and grown
in vitro in laminar flow for 14 days. The UCC were characterized by flow cytometry
(FACS), histology, immunohistochemistry, and proliferation assays and were compared
to saphenous vein-derived VC. Morphologic analysis of the UCC-seeded copolymer patches
included histology and both transmission and scanning electron microscopy. Characterization
of the extracellular matrix was performed by immunohistochemistry and quantitative
extracellular matrix protein assays. The tissue-engineered UCC patches were biomechanically
evaluated using uniaxial stress testing and were compared to native tissue.
We found that isolated UCC show a fibroblast-like morphology and superior cell growth
compared to VC. Phenotype analysis revealed positive signals for alpha-smooth muscle
actin (ASMA), desmin, and vimentin. Histology and immunohistochemistry of seeded polymers
showed layered tissue formation containing collagen I, III, and glycoaminoglycans.
Transmission electron microscopy showed viable myofibroblasts and the deposition of
collagen fibrils. A confluent tissue surface was observed during scanning electron
microscopy. Glycoaminoglycan content did not reach values of native tissue, whereas
cell content was increased. The biomechanical properties of the tissue-engineered
constructs approached native tissue values.
Tissue engineering of cardiovascular constructs using UCC is feasible in an in vitro
environment. The UCC demonstrated excellent growth properties and tissue formation
with mechanical properties approaching native tissue. It appears that UCC represent
a promising alternative autologous cell source for cardiovascular tissue engineering,
offering the additional benefits of using juvenile cells and avoiding the invasive
harvesting of intact vascular structures.