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Development of gene therapy during operation for Marfan patients

Research Project

Project/Area Number 10470271
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionYAMAGATA UNIVERSITY

Principal Investigator

SHIMAZAKI Yasuhisa  Yamagata Univ, Med, Professor, 医学部, 教授 (60116043)

Co-Investigator(Kenkyū-buntansha) WATANABE Takao  Yamagata Univ, Med, Associate Professor, 医学部, 助教授 (60138922)
INUI Kiyoshige  Yamagata Univ, Med, Assistant Professor, 医学部, 助手 (70250941)
箕輪 隆  山形大学, 医学部, 助手 (50292420)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsGene therapy / Cell transplantation / Aorta / Marfan syndrome / Marfan症候群 / パーテイクルデリバリー法 / パーティクルデリバリー
Research Abstract

We examined whether gene transfected cell transplanted into the aortic wall can survive in the tissue and change the circumference of aorta in this experiment. Thoracotomy at the 4^<th> intercostal space was carried out in the 15kg 5 adult canines under the general anesthesia. 500000 LacZ cDNA transfected canine renal cells in the 100 microlitter PBS were injected in the descending thoracic aorta. One week after the cell transplantation, canines were sacrificed. 5 excised descending thoracic aorta were fixed with the 10% buffered formalin, and then immersed in the X-Gal solution. Macroscopic findings revealed that X-Gal positive blue stained area was spread in one-third circumstances of aorta. The adventitia of the aorta showed strong reaction to X-Gal, but the media was not stained well with X-Gal. At the portion of needle insertion, not only adventitia but also media, were stained blue with X-Gal well. Then, 5 pieces of each aorta were paraffin embedded, sliced in 5-micrometer thickness and stained by HE staining for microscopic findings. Many gene transfected cells were located at the border zone between media and adventitia. Interstitial space around the transplanted cell were also stained with X-Gal, that mean the possibility of gene therapy for aortic wall by gene engineered cell transplantation. We conclude that gene engineered cell transplantation is safe and highly efficient method of gene transfection to the aorta. The fragile large vessels of Marfan patients may be treated with this new method.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

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