Microchimerism does not induce tolerance after in utero transplantation and may lead to the development of alloreactivity
Carrier E, Gilpin E, Lee TH, Busch MP, Zanetti M. J Lab Clin Med. 2000 Sep;136(3):224-35.
In utero transplantation is a new technology that may provide non-toxic treatment for congenital disorders. However, a decade of research on in utero transplantation has demonstrated a low degree of chimerism and tolerance in small and large animal models as well as in human beings. We hypothesized that if large numbers of purified stem cells/progenitors were injected, a higher degree of tolerance would be induced. We have performed a 2-year experiment designed to study chimerism and tolerance after in utero transplantation with large numbers of cytokine-recruited C-kit+ cells. Chimerism in the blood and tissues was tested through the lifespan of the animals, and in vitro immunologic assays were performed at the end of life. C-kit+ cells obtained from the peripheral blood of C57BL/6 mice were injected intraperitoneally into 12- to 13-day-old Balb/c murine fetuses. The injected populations contained 5% to 20% of Sca-1+ and 1% to 5% of CD3+ cells. Twenty-three percent of mice that received transplants showed circulating donor cells in the blood, and 7% to 14% showed donor cells in the tissues.