A double-chamber rotating bioreactor for the development of tissue-engineered hollow organs: from concept to clinical trial.
Cell and tissue engineering are now being translated into clinical organ replacement, offering alternatives to fight morbidity, organ shortages and ethico-social problems associated with allotransplantation. Central to the recent first successful use of stem cells to create an organ replacement in man was our development of a bioreactor environment. Critical design features were the abilities to drive the growth of two different cell types, to support 3D maturation, to maintain biomechanical and biological properties and to provide appropriate hydrodynamic stimuli and adequate mass transport. An analytical model was developed and applied to predict oxygen profiles in the bioreactor-cultured organ construct and in the culture media, comparing representative culture configurations and operating conditions. Autologous respiratory epithelial cells and mesenchymal stem cells (BMSCs, then differentiated into chondrocytes) were isolated, characterized and expanded. Both cell types were seeded and cultured onto a decellularized human donor tracheal matrix within the bioreactor. One year post-operatively, graft and patient are healthy, and biopsies confirm angiogenesis, viable epithelial cells and chondrocytes. Our rotating double-chamber bioreactor permits the efficient repopulation of a decellularized human matrix, a concept that can be applied clinically, as demonstrated by the successful tracheal transplantation.
Asnaghi
M Adelaide
MA
Department of Bioengineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milan, Italy. adelaide.asnaghi@mail.polimi.it
Jungebluth
Philipp
P
Raimondi
Manuela T
MT
Dickinson
Sally C
SC
Rees
Louisa E N
LE
Go
Tetsuhiko
T
Cogan
Tristan A
TA
Dodson
Amanda
A
Parnigotto
Pier Paolo
PP
Hollander
Anthony P
AP
Birchall
Martin A
MA
Conconi
Maria Teresa
MT
Macchiarini
Paolo
P
Mantero
Sara
S
D021522:Bioartificial Organs; D019149:Bioreactors; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009924:Organ Culture Techniques / Q000295:instrumentation*; D012399:Rotation; D023822:Tissue Engineering / Q000295:instrumentation*; D014132:Trachea / Q000254:growth & development* / Q000637:transplantation*; D016896:Treatment Outcome