Transplanted fetal fibroblasts: survival and distribution over time in normal adult dermis compared with autogenic, allogenic, and xenogenic adult fibroblasts.

Abstract

Cell therapy is a widely applicable therapeutic approach using cells and cell elements, frequently from fetal or young animals, for their beneficial effects. This study evaluated the host response to and tolerance of transplanted fetal skin fibroblasts. Cultured fibroblasts from adult rabbit skin (autogenic and allogenic), 21-day fetal rabbit skin (allogenic), and adult pig skin (xenogenic) were labeled with a fluorescent vital dye CM-DiI, injected intradermally into the dorsal skin of adult rabbits at multiple sites and then biopsied over an 8-week period. Each cell type showed a biphasic distribution curve with an early phase (0 to 28 days) and a late phase (28 to 56 days). In the early phase, cells showed a rise and fall in total cell density (reflecting an increase and then a decrease in total cell number), followed by a slow decrease in cell density with cells still detectable at 56 days. Fetal cells showed the highest survival at the end of the study. None of the groups showed clinical or histologic signs of acute inflammation or rejection. This study demonstrated that (1) transplanted fibroblasts are well tolerated by an immunologically competent host, (2) CM-DiI-labeled cells are detectable in vivo for at least 8 weeks, and (3) fetal fibroblasts have a distribution and survival profile that is distinct from that of adult fibroblasts.