Living, autologous pulmonary artery conduits tissue engineered from human umbilical cord cells.
BACKGROUND
Tissue engineering represents a promising approach to in vitro creation of living, autologous replacements with the potential to grow, repair, and remodel. Particularly in a congenital operation, there is a substantial need for such implantation materials. We previously demonstrated fabrication of completely autologous, functional heart valves on the basis of peripheral vascular cells. Presently the feasibility of creating pulmonary artery conduits from human umbilical cord cells was investigated.


METHODS
Human umbilical cord cells were harvested and expanded in culture. Pulmonary conduits fabricated from rapidly bioabsorbable polymers were seeded with human umbilical cord cells and grown in vitro in a pulse duplicator bioreactor. Morphologic characterization of the generated neo-tissues included histology, transmission, and scanning electron microscopy. Characterization of extracellular matrix was comprised of immunohistochemistry. Extracellular matrix protein content and cell proliferation were quantified by biochemical assays. Biomechanical testing was performed using stress-strain and burst-stress tests.


RESULTS
Histology of the conduits revealed viable, layered tissue and extracellular matrix formation with glycosaminoglycans and collagens I and III. Cells stained positive for vimentin and alpha-smooth muscle actin. Scanning electron microscopy showed confluent, homogenous tissue surfaces. Transmission electron microscopy demonstrated elements typical of viable myofibroblasts, such as collagen, fibrils, and elastin. Extracellular matrix proteins were significantly lower compared with native tissue; the cell content was increased. The mechanical strength of the pulsed constructs was comparable with native tissue; the static controls were significantly weaker.


CONCLUSIONS
In vitro fabrication of tissue-engineered human pulmonary conduits was feasible utilizing human umbilical cord cells and a biomimetic culture environment. Morphologic and mechanical features approximated human pulmonary artery. Human umbilical cord cells demonstrated excellent growth properties representing a new, readily available cell source for tissue engineering without necessitating the sacrifice of intact vascular donor structures.
Hoerstrup
Simon P
SP
Clinic for Cardiovascular Surgery, University Hospital, Zurich, Switzerland. simon_philipp.hoerstrup@chi.usz.ch
Kadner
Alexander
A
Breymann
Christian
C
Maurus
Christine F
CF
Guenter
Christina I
CI
Sodian
Ralf
R
Visjager
Jeroen F
JF
Zund
Gregor
G
Turina
Marko I
MI
D020341:Absorbable Implants; D002455:Cell Division; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005240:Feasibility Studies; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D011651:Pulmonary Artery; D013314:Stress, Mechanical; D023822:Tissue Engineering; D014182:Transplantation, Autologous; D014470:Umbilical Cord / Q000166:cytology*