Autologous valve replacement-CD133+ stem cell-plus-fibrin composite-based sprayed cell seeding for intraoperative heart valve tissue engineering.
OBJECTIVE
The development of biological valve prostheses with lifetime native-like performance and optimal host engraftment is an ultimate goal of heart valve tissue engineering. We describe a new concept for autologous graft coating based on a CD133(+)-stem-cells-plus-fibrin (SC+F) complex processed from bone marrow and peripheral blood of a single patient.


METHODS
CD133(+)-SC (1 × 10(6) cells/mL) from human bone marrow and autologous fibrin (20 mg/mL) were administered simultaneously via spray administration using the novel Vivostat Co-Delivery System. During static cultivation, SC+F performance was monitored for 20 days after delivery and compared with controls. For dynamic testing SC+F-composite was sprayed on a decellularized porcine pulmonary valve and transferred to a bioreactor under pulsatile flow conditions for 7 days.


RESULTS
Static cultivation of SC+F-composite induced significant improvements in stem cell proliferation as compared with controls. For dynamic testing, microscopic analyses on a smooth engineered heart valve surface detected homogenous distribution of stem cells. Ultrasonic analysis revealed native-like valve performance. Applied CD133(+) stem cells differentiated into endothelial-like cells positive for CD31 and vascular endothelial growth factor receptor 2 and engrafted the valve. However, occasional delamination was observed.


CONCLUSIONS
SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivo integration. However, stability remains an issue.
Kaminski
Alexander
A
Reference and Translation Center for Cardiac Stem Cell Therapy, University of Rostock, Rostock, Germany. alexander.kaminski@med.uni-rostock.de
Klopsch
Christian
C
Mark
Peter
P
Yerebakan
Can
C
Donndorf
Peter
P
Gäbel
Ralf
R
Eisert
Friederike
F
Hasken
Stefan
S
Kreitz
Sebastian
S
Glass
Aenne
A
Jockenhövel
Stefan
S
Ma
Nan
N
Kundt
Guenther
G
Liebold
Andreas
A
Steinhoff
Gustav
G
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005337:Fibrin / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006350:Heart Valve Prosthesis; D006801:Humans; D007430:Intraoperative Care; D008422:Materials Testing; D010455:Peptides / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D005337:Fibrin