TY - JOUR
T1 - Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model
AU - Marzaro, Maurizio
AU - Algeri, Mattia
AU - Tomao, Luigi
AU - Tedesco, Stefano
AU - Caldaro, Tamara
AU - Balassone, Valerio
AU - Contini, Anna Chiara
AU - Guerra, Luciano
AU - Federici D’Abriola, Giovanni
AU - Francalanci, Paola
AU - Caristo, Maria Emiliana
AU - Lupoi, Lorenzo
AU - Boskoski, Ivo
AU - Bozza, Angela
AU - Bozza, Alessandro
AU - Astori, Giuseppe
AU - Pozzato, Gianantonio
AU - Pozzato, Alessandro
AU - Costamagna, Guido
AU - Dall’Oglio, Luigi
AU - Dall'Oglio, Luigi
PY - 2020
Y1 - 2020
N2 - Background: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated. Methods: A porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering). Results: The treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one. Conclusions: A muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after seeding. The substitute was able to recapitulate in shape and function the original esophageal muscle layer.
AB - Background: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated. Methods: A porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering). Results: The treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one. Conclusions: A muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after seeding. The substitute was able to recapitulate in shape and function the original esophageal muscle layer.
KW - 3D cell culture
KW - Quantum Molecular Resonance
KW - esophagus
KW - mesenchymal stromal cells
KW - scaffold
KW - tissue engineering
KW - 3D cell culture
KW - Quantum Molecular Resonance
KW - esophagus
KW - mesenchymal stromal cells
KW - scaffold
KW - tissue engineering
UR - http://hdl.handle.net/10807/221714
U2 - 10.1177/1756284820923220
DO - 10.1177/1756284820923220
M3 - Article
SN - 1756-283X
VL - 13
SP - 175628482092322-N/A
JO - Therapeutic Advances in Gastroenterology
JF - Therapeutic Advances in Gastroenterology
ER -