Development of abnormal tissue architecture in transplanted neonatal rat myocytes.
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.
Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. peter.whittaker@umassmed.edu
Peter
P
Whittaker
Jochen
J
Müller-Ehmsen
Joan S
JS
Dow
Larry H
LH
Kedes
Robert A
RA
Kloner
D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000648:ultrastructure; D017690:Cell Transplantation; D003094:Collagen / Q000648:ultrastructure; D005260:Female; D006352:Heart Ventricles; D008297:Male; D008859:Microscopy, Polarization; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000166:cytology* / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344
D003094:Collagen