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Development of abnormal tissue architecture in transplanted neonatal rat myocytes
Peter Whittaker1, Jochen Müller-Ehmsen, Joan S Dow
1Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. peter.whittaker@umassmed.edu
Background:
Most myocardial cell transplant studies focus on demonstration of improved function; however, such improvement depends on the development of appropriate tissue structure. Thus, our aim was to assess the architectural changes that occurred after cell transplant into normal and infarcted myocardium.
Methods:
Male neonatal cells (1 to 2 days old) were injected into the left ventricular free wall of adult female rats. The tissue was examined 0 to 1 days and 1 to 2, 4 to 6, and 12 weeks later in noninfarcted hearts and 6 months after transplant into infarcts. In histologic sections, we assessed the cells' retardation of polarized light (to measure development of contractile elements), two-dimensional cell orientation, cell nuclear morphology, and collagen content.
Results:
The transplant cells' retardation of polarized light gradually increased to 81% of that of host cells after 6 months (p < 0.001). The transplant cells were disorganized and although their nuclei increased in size, they always had a rounded appearance. Collagen content in the transplant was 210% to 430% higher than in host tissue (p < 0.01). In addition, scar collagen always separated transplant and host cells.
Conclusions:
One architectural feature, the rounded nuclei, provided a distinctive marker to identify transplanted cells. Nevertheless, the transplants' inhibited muscle development together with disorganization, separation from the host muscle, and a substantial increase in collagen resulted in a structure unlikely to play an active role in systolic function.