Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective
Objectives: Palliative treatment of cyanotic congenital heart disease (CCHD) uses systemic-to-pulmonary conduits, often a modified Blalock–Taussig–Thomas shunt (mBTTs). Expanded polytetrafluoroethylene (ePTFE) mBTTs have associated risks for thrombosis and infection. The Human Acellular Vessel (HAV)...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | JTCVS Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666273623002085 |
| _version_ | 1827807284553580544 |
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| author | Kevin M. Nash, PhD Brian A. Boe, MD Sergio A. Carrillo, MD Andrew Harrison, AS, ARRT Ryuma Iwaki, MD John Kelly, MD Robert D. Kirkton, PhD Ramkumar Krishnamurthy, PhD Jeffrey H. Lawson, MD, PhD Yuichi Matsuzaki, MD, PhD Heather L. Prichard, PhD Kejal Shah, MD Toshiharu Shinoka, MD, PhD Christopher K. Breuer, MD |
| author_facet | Kevin M. Nash, PhD Brian A. Boe, MD Sergio A. Carrillo, MD Andrew Harrison, AS, ARRT Ryuma Iwaki, MD John Kelly, MD Robert D. Kirkton, PhD Ramkumar Krishnamurthy, PhD Jeffrey H. Lawson, MD, PhD Yuichi Matsuzaki, MD, PhD Heather L. Prichard, PhD Kejal Shah, MD Toshiharu Shinoka, MD, PhD Christopher K. Breuer, MD |
| author_sort | Kevin M. Nash, PhD |
| collection | DOAJ |
| description | Objectives: Palliative treatment of cyanotic congenital heart disease (CCHD) uses systemic-to-pulmonary conduits, often a modified Blalock–Taussig–Thomas shunt (mBTTs). Expanded polytetrafluoroethylene (ePTFE) mBTTs have associated risks for thrombosis and infection. The Human Acellular Vessel (HAV) (Humacyte, Inc) is a decellularized tissue-engineered blood vessel currently in clinical trials in adults for vascular trauma, peripheral artery disease, and end-stage renal disease requiring hemodialysis. In addition to restoring blood flow, the engineered HAV demonstrates the capacity for host cellular remodeling into native-like vasculature. Here we report preclinical evaluation of a small-diameter (3.5 mm) HAV as a mBTTs in a non-human primate model. Methods: We implanted 3.5 mm HAVs as right subclavian artery to pulmonary artery mBTTs in non-immunosuppressed juvenile rhesus macaques (n = 5). HAV patency, structure, and blood flow were assessed by postoperative imaging from 1 week to 6 months. Histology of HAVs and surrounding tissues was performed. Results: Surgical procedures were well tolerated, with satisfactory anastomoses, showing feasibility of using the 3.5 mm HAV as a mBTTs. All macaques had some immunological reactivity to the human extracellular matrix, as expected in this xenogeneic model. HAV mBTTs remained patent for up to 6 months in animals, exhibiting mild immunoreactivity. Two macaques displaying more severe immunoreactivity to the human HAV material developed midgraft dilatation without bleeding or rupture. HAV repopulation by host cells expressing smooth muscle and endothelial markers was observed in all animals. Conclusions: These findings may support use of 3.5 mm HAVs as mBTTs in CCHD and potentially other pediatric vascular indications. |
| first_indexed | 2024-03-11T21:55:12Z |
| format | Article |
| id | doaj.art-dbfdc050eeff4efa8d573ed68bec9a99 |
| institution | Directory Open Access Journal |
| issn | 2666-2736 |
| language | English |
| last_indexed | 2024-03-11T21:55:12Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTCVS Open |
| spelling | doaj.art-dbfdc050eeff4efa8d573ed68bec9a992023-09-26T04:12:39ZengElsevierJTCVS Open2666-27362023-09-0115433445Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspectiveKevin M. Nash, PhD0Brian A. Boe, MD1Sergio A. Carrillo, MD2Andrew Harrison, AS, ARRT3Ryuma Iwaki, MD4John Kelly, MD5Robert D. Kirkton, PhD6Ramkumar Krishnamurthy, PhD7Jeffrey H. Lawson, MD, PhD8Yuichi Matsuzaki, MD, PhD9Heather L. Prichard, PhD10Kejal Shah, MD11Toshiharu Shinoka, MD, PhD12Christopher K. Breuer, MD13Humacyte, Inc, Durham, NCThe Heart Center, Nationwide Children’s Hospital, Columbus, OhioDepartment of Cardiothoracic Surgery, Nationwide Children’s Hospital, Columbus, OhioThe Heart Center, Nationwide Children’s Hospital, Columbus, OhioCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OhioThe Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OhioHumacyte, Inc, Durham, NCDepartment of Radiology, Nationwide Children’s Hospital, Columbus, OhioHumacyte, Inc, Durham, NC; Department of Surgery, Duke University, Durham, NCCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OhioHumacyte, Inc, Durham, NCCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OhioThe Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Department of Cardiothoracic Surgery, Nationwide Children’s Hospital, Columbus, Ohio; Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OhioCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, Nationwide Children’s Hospital, Columbus, Ohio; Address for reprints: Christopher K. Breuer, MD, Nationwide Children’s Hospital, Tissue Engineering Program and Surgical Research, 700 Children’s Dr, WB4151, Columbus, OH 43205-2664.Objectives: Palliative treatment of cyanotic congenital heart disease (CCHD) uses systemic-to-pulmonary conduits, often a modified Blalock–Taussig–Thomas shunt (mBTTs). Expanded polytetrafluoroethylene (ePTFE) mBTTs have associated risks for thrombosis and infection. The Human Acellular Vessel (HAV) (Humacyte, Inc) is a decellularized tissue-engineered blood vessel currently in clinical trials in adults for vascular trauma, peripheral artery disease, and end-stage renal disease requiring hemodialysis. In addition to restoring blood flow, the engineered HAV demonstrates the capacity for host cellular remodeling into native-like vasculature. Here we report preclinical evaluation of a small-diameter (3.5 mm) HAV as a mBTTs in a non-human primate model. Methods: We implanted 3.5 mm HAVs as right subclavian artery to pulmonary artery mBTTs in non-immunosuppressed juvenile rhesus macaques (n = 5). HAV patency, structure, and blood flow were assessed by postoperative imaging from 1 week to 6 months. Histology of HAVs and surrounding tissues was performed. Results: Surgical procedures were well tolerated, with satisfactory anastomoses, showing feasibility of using the 3.5 mm HAV as a mBTTs. All macaques had some immunological reactivity to the human extracellular matrix, as expected in this xenogeneic model. HAV mBTTs remained patent for up to 6 months in animals, exhibiting mild immunoreactivity. Two macaques displaying more severe immunoreactivity to the human HAV material developed midgraft dilatation without bleeding or rupture. HAV repopulation by host cells expressing smooth muscle and endothelial markers was observed in all animals. Conclusions: These findings may support use of 3.5 mm HAVs as mBTTs in CCHD and potentially other pediatric vascular indications.http://www.sciencedirect.com/science/article/pii/S2666273623002085congenital heart diseasetissue-engineered vascular graftsBlalock–Taussig-Thomas shunt |
| spellingShingle | Kevin M. Nash, PhD Brian A. Boe, MD Sergio A. Carrillo, MD Andrew Harrison, AS, ARRT Ryuma Iwaki, MD John Kelly, MD Robert D. Kirkton, PhD Ramkumar Krishnamurthy, PhD Jeffrey H. Lawson, MD, PhD Yuichi Matsuzaki, MD, PhD Heather L. Prichard, PhD Kejal Shah, MD Toshiharu Shinoka, MD, PhD Christopher K. Breuer, MD Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective JTCVS Open congenital heart disease tissue-engineered vascular grafts Blalock–Taussig-Thomas shunt |
| title | Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective |
| title_full | Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective |
| title_fullStr | Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective |
| title_full_unstemmed | Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective |
| title_short | Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective |
| title_sort | evaluation of tissue engineered human acellular vessels as a blalock taussig thomas shunt in a juvenile primate modelcentral messageperspective |
| topic | congenital heart disease tissue-engineered vascular grafts Blalock–Taussig-Thomas shunt |
| url | http://www.sciencedirect.com/science/article/pii/S2666273623002085 |
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