TY - JOUR
T1 - First-in-Human Segmental Esophageal Reconstruction Using a Bioengineered Mesenchymal Stromal Cell–Seeded Implant
AU - Aho, Johnathon M.
AU - La Francesca, Saverio
AU - Olson, Scott D.
AU - Triolo, Fabio
AU - Bouchard, Jeff
AU - Mondano, Laura
AU - Sundaram, Sumati
AU - Roffidal, Christina
AU - Cox, Charles S.
AU - Wong Kee Song, Louis Michel
AU - Said, Sameh M.
AU - Fodor, William
AU - Wigle, Dennis A.
N1 - Funding Information:
Dr. Aho was supported by a grant from the National Heart, Lung, and Blood Institute . T32 HL105355. Funding for the study and materials was provided by Biostage Inc. The funders had no role in the design or conduct of the study and management of the patient or collection of patient samples at autopsy. All authors, including Biostage scientists, participated in data analysis and the preparation of the manuscript and figures. The authors also acknowledge Sherif Soliman, PhD, Debra Buxton, Deepa Bhattarai, Sufira Kiran, Cecilia Martin, Karthik Prabhakara, and Naama Toledano-Furman. This study was approved by the Food and Drug Administration under the Expanded Access Use—Individual Patient Emergency, 21 Code of Federal Regulations 312.310(d); Emergency Investigational New Drug #17402 (issued to Dr. Wigle and the Mayo Clinic, Rochester, MN). This work was performed under the Mayo Clinic Institutional Review Board Approval, Food and Drug Administration Compassionate use exemption, consistent with the Declaration of Helsinki.
Funding Information:
Dr. Aho was supported by a grant from the National Heart, Lung, and Blood Institute. T32 HL105355. Funding for the study and materials was provided by Biostage Inc. The funders had no role in the design or conduct of the study and management of the patient or collection of patient samples at autopsy. All authors, including Biostage scientists, participated in data analysis and the preparation of the manuscript and figures. The authors also acknowledge Sherif Soliman, PhD, Debra Buxton, Deepa Bhattarai, Sufira Kiran, Cecilia Martin, Karthik Prabhakara, and Naama Toledano-Furman. This study was approved by the Food and Drug Administration under the Expanded Access Use?Individual Patient Emergency, 21 Code of Federal Regulations 312.310(d); Emergency Investigational New Drug #17402 (issued to Dr. Wigle and the Mayo Clinic, Rochester, MN). This work was performed under the Mayo Clinic Institutional Review Board Approval, Food and Drug Administration Compassionate use exemption, consistent with the Declaration of Helsinki.
Publisher Copyright:
© 2021 The Authors
PY - 2021/9
Y1 - 2021/9
N2 - Introduction: Resection and reconstruction of the esophagus remains fraught with morbidity and mortality. Recently, data from a porcine reconstruction model revealed that segmental esophageal reconstruction using an autologous mesenchymal stromal cell-seeded polyurethane graft (Cellspan esophageal implant [CEI]) can facilitate esophageal regrowth and regeneration. To this end, a patient requiring a full circumferential esophageal segmental reconstruction after a complex multiorgan tumor resection was approved for an investigational treatment under the Food and Drug Administration Expanded Access Use (Investigational New Drug 17402). Methods: Autologous adipose-derived mesenchymal stromal cells (Ad-MSCs) were isolated from the Emergency Investigational New Drug patient approximately 4 weeks before surgery from an adipose tissue biopsy specimen. The Ad-MSCs were grown and expanded under current Good Manufacturing Practice manufacturing conditions. The cells were then seeded onto a polyurethane fiber mesh scaffold (Cellspan scaffold) and cultured in a custom bioreactor to manufacture the final CEI graft. The cell-seeded scaffold was then shipped to the surgical site for surgical implantation. After removal of a tumor mass and a full circumferential 4 cm segment of the esophagus that was invaded by the tumor, the CEI was implanted by suturing the tubular CEI graft to both ends of the remaining native esophagus using end-to-end anastomosis. Results: In this case report, we found that a clinical-grade, tissue-engineered esophageal graft can be used for segmental esophageal reconstruction in a human patient. This report reveals that the graft supports regeneration of the esophageal conduit. Histologic analysis of the tissue postmortem, 7.5 months after the implantation procedure, revealed complete luminal epithelialization and partial esophageal tissue regeneration. Conclusions: Autologous Ad-MSC seeded onto a tubular CEI tissue-engineered graft stimulates tissue regeneration following implantation after a full circumferential esophageal resection.
AB - Introduction: Resection and reconstruction of the esophagus remains fraught with morbidity and mortality. Recently, data from a porcine reconstruction model revealed that segmental esophageal reconstruction using an autologous mesenchymal stromal cell-seeded polyurethane graft (Cellspan esophageal implant [CEI]) can facilitate esophageal regrowth and regeneration. To this end, a patient requiring a full circumferential esophageal segmental reconstruction after a complex multiorgan tumor resection was approved for an investigational treatment under the Food and Drug Administration Expanded Access Use (Investigational New Drug 17402). Methods: Autologous adipose-derived mesenchymal stromal cells (Ad-MSCs) were isolated from the Emergency Investigational New Drug patient approximately 4 weeks before surgery from an adipose tissue biopsy specimen. The Ad-MSCs were grown and expanded under current Good Manufacturing Practice manufacturing conditions. The cells were then seeded onto a polyurethane fiber mesh scaffold (Cellspan scaffold) and cultured in a custom bioreactor to manufacture the final CEI graft. The cell-seeded scaffold was then shipped to the surgical site for surgical implantation. After removal of a tumor mass and a full circumferential 4 cm segment of the esophagus that was invaded by the tumor, the CEI was implanted by suturing the tubular CEI graft to both ends of the remaining native esophagus using end-to-end anastomosis. Results: In this case report, we found that a clinical-grade, tissue-engineered esophageal graft can be used for segmental esophageal reconstruction in a human patient. This report reveals that the graft supports regeneration of the esophageal conduit. Histologic analysis of the tissue postmortem, 7.5 months after the implantation procedure, revealed complete luminal epithelialization and partial esophageal tissue regeneration. Conclusions: Autologous Ad-MSC seeded onto a tubular CEI tissue-engineered graft stimulates tissue regeneration following implantation after a full circumferential esophageal resection.
KW - Artificial organ
KW - Esophageal reconstruction
KW - Esophageal replacement
KW - Tissue engineered graft
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U2 - 10.1016/j.jtocrr.2021.100216
DO - 10.1016/j.jtocrr.2021.100216
M3 - Article
AN - SCOPUS:85122708700
VL - 2
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
SN - 2666-3643
IS - 9
M1 - 100216
ER -