Local Release of VEGF Using Fiber Mats Enables Effective Transplantation of Layered Cardiomyocyte Sheets

• Published in: Macromolecular bioscience Vol. 17; no. 8
• Main Authors: Nagase, Kenichi, Nagumo, Yuhei, Kim, Miri, Kim, Hee‐Jung, Kyung, Hei‐Won, Chung, Hye‐Jin, Sekine, Hidekazu, Shimizu, Tatsuya, Kanazawa, Hideko, Okano, Teruo, Lee, Seung‐Jin, Yamato, Masayuki
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.08.2017
• Subjects: Animals; Blood vessels; Cardiomyocytes; cell sheet; Cells, Immobilized - cytology; Cells, Immobilized - metabolism; Cells, Immobilized - transplantation; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; electrospun fiber; Erythrocytes; Gangrene; Glycolic acid; Growth factors; Lactic Acid - chemistry; Lactic Acid - pharmacology; Mats; Membranes, Artificial; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - transplantation; Nanoparticles; Necrosis; Nutrients; Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacology; Polyvinyl alcohol; Rats; Rats, Nude; regenerative medicine; Releasing; Rodents; Therapeutic applications; Tissue engineering; Transplantation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - chemistry; Vascular Endothelial Growth Factor A - pharmacology; Vascular endothelial growth factor receptors; Vascularization; VEGF; electrospun fiber; tissue engineering; VEGF; regenerative medicine; cell sheet
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201700073

Cell sheet transplantation is a key tissue engineering technology. A vascular endothelial growth factor (VEGF)‐releasing fiber mat is developed for the transplantation of multilayered cardiomyocyte sheets. Poly(vinyl alcohol) fiber mats bearing poly(lactic‐co‐glycolic acid) nanoparticles that incorporate VEGF are fabricated using electrospinning and electrospray methods. Six‐layered cardiomyocyte sheets are transplanted with a VEGF‐releasing mat into athymic rats. After two weeks, these sheets produce thicker cardiomyocyte layers compared with controls lacking a VEGF‐releasing mat, and incorporate larger‐diameter blood vessels containing erythrocytes. Thus, local VEGF release near the transplanted cardiomyocytes induces vascularization, which supplies sufficient oxygen and nutrients to prevent necrosis. In contrast, cardiomyocyte sheets without a VEGF‐releasing mat do not survive in vivo, probably undergo necrosis, and are reduced in thickness. Hence, these VEGF‐releasing mats enable the transplantation of multilayered cardiomyocyte sheets in a single procedure, and should expand the potential of cell sheet transplantation for therapeutic applications. Development of a vascular endothelial growth factor (VEGF)‐releasing fiber mat that allows for the effective transplantation of multilayered cardiomyocyte sheets in a single procedure is shown. Local supply of VEGF to cardiomyocyte sheets enhances their vascularization in vivo, overcoming necrosis and leading to improved survival. These VEGF‐releasing mats therefore expand the use of cell sheet transplantation for potential therapeutic applications.