| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ann Thorac Surg 1999;68:2305
© 1999 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, Collis Cardiac Surgical Research Laboratory, Brown University School of Medicine, Providence, RI 02903, USA
Invited commentary
This paper by Dr. Shum-Tim and his colleagues is a seminal contribution in the field of bioengineering of cardiovascular tissues. Since Alexis Carrel first demonstrated that blood vessels could be sutured and replaced, the ideal arterial conduit has been sought. After decades of materials, devices, and surfaces research, there is consensus that the ideal replacement vessel needs to be living and constructed with cells that know their job and are comfortable in their environment. This current report represents a significantly different approach than that reported by the Laval University Group (Quebec City) in the FASEB Journal in 1998 [1]. The Canadian group created a tissue engineered human blood vessel by first growing sheets of cells (endothelial and matrix) and then constructed the three dimensional vessel by rolling the tissue layers together around a tubular mandrel. The Harvard-MIT approach used a synthetic biodegradable polymer scaffold that was seeded with a mixed cell culture of cardiovascular cells obtained from the carotid artery of the ultimate recipient. The success by Dr. Shum-Tim and his colleagues contains a number of important lessons for both the research and clinical community.
The authors describe the use of a biodegradable polyglactin-polyglycolic acid-polyhydroxyalkanoate co-polymer, which was seeded in vitro and then reimplanted into the recipient abdominal aortic position of juvenile lambs. As compared to the unseeded control group, these engineered tissues were resistant to thrombotic failure, appeared to develop a relatively normal multi-layer histology and, the demonstration of the presence of MMP-2 gelatinases suggested that remodeling capability was retained. Many different seeding strategies have been tried by various researchers around the world spanning the range from sequential in vitro monoculture cell seedings to in vivo autologous migration. This paper suggests that the technically simpler mixed cell seeding in vitro phase is feasible and required. This validates the concept of an actively bioengineered cardiovascular tissue replacement.
Importantly, the authors of this study also performed stress-strain mechanical testing which they reported as resembling and approaching the native aorta "over time." Such definition of material properties will be necessary to advance such techniques to the clinical setting for both practical and regulatory reasons. Other key questions include defining the optimal scaffolding material (in this case a biodegradable polymer), ascertaining the correct cells to use, learning how to derive appropriate phenotypic expression, develop optimal implantation/reconstruction surgical techniques, develop methods to monitor and modulate cell-cell signaling, etc, etc.
Such work is only beginning to access the capability of cellular engineering particularly when augmented by future techniques involving genetic manipulation of the cells engineered into new positions. Many additional practical and basic questions will need to be addressed and many new discoveries accomplished in the laboratory as we travel this path to the ultimate permanent cardiovascular replacement tissue that will have the capabilities of growth, repair and regeneration as well as retaining the requisite mechanical properties of the cardiovascular tissue being replaced. The fact that so many different laboratories are utilizing fundamentally different approaches makes the field exciting and one applauds each success as it occurs.
References
Related Article
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
