Ischemic central necrosis in pockets of transplanted myoblasts in nonhuman primates: Implications for cell-transplantation strategies

Background. Several cell-transplantation strategies implicate the injection of cells into tissues. Avascular accumulations of implanted cells are then formed. Because the diffusion of oxygen and nutrients from the surrounding tissue throughout the implanted cell accumulations may be limited, central ischemic necrosis could develop. We analyzed this possibility after myoblast transplantation in nonhuman primates. Methods. Macaca monkeys were injected intramuscularly with different amounts of myoblasts per single site. These sites were sampled 1hr later and at posttransplantation days 1, 3, 5, and 7 and analyzed by histological techniques. Results. One day posttransplantation, the largest pockets of implanted cells showed cores of massive necrosis. The width of the peripheral layer of living cells was similar to 100 -200 mu m. We thus analyzed the relationship between the amount of myoblasts injected per site and the volume of ischemic necrosis. Delivering 0.1 X 10(6) and 0.3 X 10(6) myoblasts did not produce ischemic necrosis; pockets of 1 X 10(6), 3X 10(6), 10 X 10(6) and 20X 10(6) myoblasts exhibited, respectively, a mean of 2%, 9%, 41%, and 59% of central necrosis. Intense macrophage infiltration took place in the muscle, invading the accumulations of necrotic cells and eliminating them by posttransplantation days 5 to 7. Conclusions. The desire to create more neoformed tissue by delivering more cells per injection site is confronted with the fact that the acute survival of the implanted cells is restricted to the peripheral layer that can profit of the diffusion of oxygen and nutriments from the surrounding recipient's tissue.