Original article: cardiovascular
Autologous smooth muscle cell transplantation improved heart function in dilated cardiomyopathy

Presented at the Thirty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.
https://doi.org/10.1016/S0003-4975(00)01630-1Get rights and content

Abstract

Background. Transplantation of myocytes into scarred myocardium has been shown to inhibit ventricular remodeling and maintain myocardial contractility. However, the effect of cell transplantation on hearts with global rather than regional dysfunction is unknown. Therefore, we evaluated the effect of transplantation of autologous smooth muscle cells on the morphometry and function of dilated cardiomyopathic hearts.

Methods. Smooth muscle cells were isolated from the ductus deferens of 13-week-old BIO 53.58 hamsters with dilated cardiomyopathy, and cultured for 4 weeks before transplantation. Smooth muscle cells (4 × 106 cells) or culture medium were injected into 17-week-old animals in the transplantation and control groups (n = 12 each), respectively. Prelabeling of the smooth muscle cells with 5-bromo-2′-deoxyuridine was performed before transplantation in a group of transplanted hamsters. Another group (sham, n = 12) underwent the operation but did not receive an injection either of smooth muscle cells or of culture medium. Four weeks after transplantation, heart function was evaluated in a Langendorff preparation.

Results. Musclelike tissue, labeled with 5-bromo-2′-deoxyuridine, was found at the site of transplantation in the cell-transplanted animals. The cell-transplanted hearts were smaller (p < 0.001), and had greater developed pressures and maximum rate of increase of left ventricular pressure (both p < 0.001) than control and sham hearts. Control hamsters injected with culture medium did not differ from sham-operated animals.

Conclusions. Transplantation of autologous smooth muscle cells prevented cardiac dilatation and improved ventricular function in hamsters with dilated cardiomyopathy.

Section snippets

Experimental animals

The experimental animals used were male BIO 53.58 hamsters (BIO Breeders, Fitchburg, MA) weighing approximately 100 g. All procedures on these hamsters were approved by the Animal Care Committee of the Toronto General Hospital, and carried out in compliance with the “Guide to the Care and Use of Experimental Animals” of the Canadian Council on Animal Care and the “Guide for the Care and Use of Laboratory Animals” published by the National Institutes of Health (NIH publication 85-23, revised

Purity and labeling of cultured smooth muscle cells

The purity of the cultured smooth muscle cells, defined as positive immunohistochemical staining for α-smooth muscle actin, was 87.8% ± 3.4% (n = 6) just before transplantation (Fig 1). The efficiency of labeling with BrdU was 48.6% ± 6.5% (n = 2).

Histology

Severe focal myocardial necrosis and fibrosis were noted throughout the myocardium of the 21-week-old hamsters in all groups (Fig 2A). Four weeks after smooth muscle cell transplantation, a block of musclelike tissue was noted at the site of

Comment

Since the initial studies in which cultured AT-1 and fetal cardiomyocytes were transplanted into syngeneic mouse hearts 14, 15, significant progress has been achieved in the field of cell transplantation. Transplantation of cultured fetal and neonatal cardiomyocytes 5, 6, 7, skeletal muscle satellite cells 8, 9, and smooth muscle cells [10] has been shown to improve the function of scarred and infarcted hearts. Previously, we have evaluated the effect of allotransplantation of heart cells in

Acknowledgements

We thank Dev Olshansky and James C. Ho for the preparation and staining of the histologic materials and Drs Eung-Joong Kim and Shinji Tomita for surgical assistance. Ren-Ke Li is a Research Scholar of the Heart and Stroke Foundation of Canada. Richard D. Weisel is a Career Investigator of the Heart and Stroke Foundation of Ontario. This research was supported by Ren-Ke Li’s research grants from the Medical Research Council of Canada (MT-13665).

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