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      Tissue-Engineered Blood Vessels in Pediatric Cardiac Surgery

      review-article
      , MD * , , MD
      The Yale Journal of Biology and Medicine
      Yale Journal of Biology and Medicine

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          Abstract

          Pediatric cardiovascular surgeons often encounter patients requiring surgical intervention utilizing foreign materials to repair complex lesions. However, the materials that are commonly used lack growth potential, and long-term results have revealed several material-related failures, such as stenosis, thromboembolization, calcium deposition, and risk of infection. To solve these problems, in particular for children who require the implantation of dynamic material with growth potential, we sought to develop optimal filling materials with biocompatibility and growth potential. Previously, we reported the advantages of tissue-engineered vascular autografts (TEVAs) in animal models and in human clinical applications utilizing autologous cells and biodegradable scaffolds. The key benefits from utilizing such scaffolds is that they degrade in vivo, thereby avoiding the long-term presence of foreign ma-terials, and the seeded cells proliferate and differentiate to construct new tissue.

          Recent studies have demonstrated the existence of bone marrow-derived endothelial pro-genitor cells that contribute to vasculogenesis and angiogenesis and the successful endothelialization of artificial grafts using bone marrow cells. We provided evidence that bone marrow cells as a source for seeding onto a biodegradable scaffold are useful and that seeded cells contribute to the histogenesis of TEVAs. Therefore, we applied this technique in clinical trials with good results. In this review article, we provide an overview of our work developing “tissue-engineered blood vessels” created by utilizing autologous mononuclear bone marrow cells.

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          Most cited references21

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          Tissue engineering.

          The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care. A new field, tissue engineering, applies the principles of biology and engineering to the development of functional substitutes for damaged tissue. This article discusses the foundations and challenges of this interdisciplinary field and its attempts to provide solutions to tissue creation and repair.
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            Successful application of tissue engineered vascular autografts: clinical experience.

            Foreign materials often used in cardiovascular surgery may cause unwanted side effects and reduced growth potential. To resolve these problems, we have designed a tissue-engineering technique that utilizes bone marrow cells (BMCs) in clinical treatments. To obtain tissue-engineered material, we harvested saphenous vein samples from patients, which were then minced, cultured and seeded onto a biodegradable scaffold. The first operation was performed in May 1999 as previously described (N. Engl. J. Med. 344 (7) (2001) 532) and this method was repeated on two other patients. From November 2001, we used aspirated BMCs as the cell source, which were seeded onto the scaffold on the day of surgery. This method was applied in 22 patients. There was no morbidity such as thrombogenic complications, stenosis or obstruction of tissue-engineered autografts, and no mortality due to these techniques. These results indicate that BMCs seeded onto a biodegradable scaffold to establish tissue-engineered vascular autografts (TEVAs) is an ideal strategy, and present strong evidence for the justification and validity of our protocol in clinical trials of tissue engineering.
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              First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo.

              Materials commonly used to repair complex cardiac defects lack growth potential and have other unwanted side effects. We designed and tested a bone marrow cell (BMC)-seeded biodegradable scaffold that avoids these problems. To demonstrate the contribution of the BMCs to histogenesis, we labeled them with green fluorescence, seeded them onto scaffolds, and implanted them in the inferior vena cava of dogs. The implanted grafts were analyzed immunohistochemically at 3 hours and subsequently at 2, 4, and 8 weeks after implantation using antibodies against endothelial cell lineage markers, endothelium, and smooth muscle cells. There was no stenosis or obstruction caused by the tissue-engineered vascular autografts (TEVAs) implanted into the dogs. Immunohistochemically, the seeded BMCs expressing endothelial cell lineage markers, such as CD34, CD31, Flk-1, and Tie-2, adhered to the scaffold. This was followed by proliferation and differentiation, resulting in expression of endothelial cells markers, such as CD146, factor VIII, and CD31, and smooth muscle cell markers, such as alpha-smooth muscle cell actin, SMemb, SM1, and SM2. Vascular endothelial growth factor and angiopoietin-1 were also produced by cells in TEVAs. These results provide direct evidence that the use of BMCs enables the establishment of TEVAs. These TEVAs are useful for cardiovascular surgery in humans and especially in children, who require biocompatible materials with growth potential, which might reduce the instance of complications caused by incompatible materials and lead to a reduced likelihood of further surgery.
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                Author and article information

                Journal
                Yale J Biol Med
                The Yale Journal of Biology and Medicine
                Yale Journal of Biology and Medicine
                0044-0086
                1551-4056
                December 2008
                December 2008
                : 81
                : 4
                : 161-166
                Affiliations
                Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
                Author notes
                [* ]To whom all correspondence should be addressed: Toshiharu Shinoka, MD, Department of Surgery, Yale University School of Medicine, 333 Cedar Street, Room 121 FMB, P.O. Box 208039, New Haven, CT 06520-8039; Tele: 203-785-2702; Fax: 203-785-3346; E-mail: toshiharu.shinoka@ 123456yale.edu .
                Article
                2605305
                19099046
                4a4dfd07-4c34-4eaf-aaa4-d3b8d63d7c7a
                Copyright ©2008, Yale Journal of Biology and Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way.

                History
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                Review
                Surgery Issue

                Medicine
                Medicine

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