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(Circulation. 2004;110:324-329.)
© 2004 American Heart Association, Inc.

Original Articles

Implantation of Immature Neonatal Cardiac Cells Into the Wall of the Aorta in Rats

A Novel Model for Studying Morphological and Functional Development of Heart Cells in an Extracardiac Environment

Wangde Dai, MD; Sharon L. Hale, BS; Robert A. Kloner, MD, PhD

From The Heart Institute, Good Samaritan Hospital, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, California.

Correspondence to Robert A. Kloner, The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017. E-mail Rkloner{at}goodsam.org

Received October 21, 2003; de novo received February 2, 2004; revision received April 1, 2004; accepted April 5, 2004.

Background— Morphological and functional development of implanted neonatal cardiac cells in the wall of the abdominal aorta in rats was investigated.

Methods and Results— Cardiomyocytes from neonatal Fischer rats (both sexes) or medium were injected into the wall of the abdominal aorta in female Fischer rats (n=22 in each group). Two or 6 weeks later, the grafted site was exposed and fixed for histological and immunohistological examination. Polymerase chain reaction analysis of the SRY gene to identify male cells was performed in the treated aortas. Seven of 10 cell-treated aortas but none of 10 medium-treated aortas showed spontaneous rhythmic beating at the grafted site after excision of the heart at 2 weeks. Polymerase chain reaction of the SRY gene was positive in 3 cell-treated aortas and none of 3 medium-treated aortas at 6 weeks. Hematoxylin-and-eosin staining showed viable grafts in 9 of 10 aortas at 2 weeks and 9 of 9 aortas at 6 weeks in the cell-treated group but in none of the aortas receiving medium. Neonatal cardiomyocytes in the graft formed compact, longitudinally oriented cardiac muscle bundles and had cross-striations and vascularization. Immunohistochemical staining for sarcomeric actin was positive in 4 of 10 aortas at 2 weeks and 9 of 9 aortas at 6 weeks in the cell group but in none of the aortas in the medium group.

Conclusions— Grafted neonatal cardiomyocytes survive, differentiate, grow, develop a blood supply, and spontaneously contract within the wall of the aorta in rats.

Key Words: aorta • grafting • cells • transplantation

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