Evaluation of tissue-engineered human acellular vessels as a Blalock–Taussig–Thomas shunt in a juvenile primate modelCentral MessagePerspective
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
Affiliations
Kevin M. Nash, PhD
Humacyte, Inc, Durham, NC
Brian A. Boe, MD
The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio
Sergio A. Carrillo, MD
Department of Cardiothoracic Surgery, Nationwide Children’s Hospital, Columbus, Ohio
Andrew Harrison, AS, ARRT
The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio
Ryuma Iwaki, MD
Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, Ohio
John Kelly, MD
The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, Ohio
Robert D. Kirkton, PhD
Humacyte, Inc, Durham, NC
Ramkumar Krishnamurthy, PhD
Department of Radiology, Nationwide Children’s Hospital, Columbus, Ohio
Jeffrey H. Lawson, MD, PhD
Humacyte, Inc, Durham, NC; Department of Surgery, Duke University, Durham, NC
Yuichi Matsuzaki, MD, PhD
Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, Ohio
Heather L. Prichard, PhD
Humacyte, Inc, Durham, NC
Kejal Shah, MD
Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, Ohio
Toshiharu Shinoka, MD, PhD
The 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, Ohio
Christopher K. Breuer, MD
Center 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.
