The use of CD34⁺ mobilized peripheral blood as a donor cell source does not improve chimerism after in utero hematopoietic stem cell transplantation in non‐human primates

Abstract

In utero hematopoietic stem cell transplantation is a therapeutic procedure that could potentially cure many developmental diseases affecting the immune and hematopoietic systems. In most clinical and experimental settings of fetal hematopoietic transplantation the level of donor cell engraftment has been low, suggesting that even in the fetus there are significant barriers to donor cell engraftment. In postnatal hematopoietic transplantation donor cells obtained from mobilized peripheral blood engraft more rapidly than cells derived from marrow. We tested the hypothesis that use of donor hematopoietic/stem cells obtained from mobilized peripheral blood would improve engraftment and the level of chimerism after in utero transplantation in non-human primates. Despite the potential competitive advantage from the use of CD 34(+) from mobilized peripheral blood, the level of chimerism was not appreciably different from a group of animals receiving marrow-derived CD 34(+) donor cells. Based on these results, it is unlikely that this single change in cell source will influence the clinical outcome of fetal hematopoietic transplantation.

Experimental and clinical progress of in utero hematopoietic cell transplantation therapy for congenital disorders

“…Finally, low levels of allogeneic chimerism were also achieved in non-human primates (Michejda et al, 1992;Asano et al, 2003;Shields et al, 2003;Mahieu-Caputo et al, 2004;Shields et al, 2004;Shields et al, 2005) (Table 5). Fetal immune suppression resulted in an increased level of chimerism, but the level remained low (Shields et al, 2004).…”

In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

“… 15 , 40 , 90 , 91 IUTx has also been successfully performed in goats 92 , 93 and pigs, 40 and low levels of engraftment have been achieved in nonhuman primates. 93–99 Subsequent studies in the pig model provided compelling evidence that induction of immune tolerance in the fetus is highly beneficial for postnatal solid organ transplantation, as IUTx of adult BM-derived HSC in fetal swine prolonged the survival of a kidney allograft. 100 These studies thus provide important experimental support for the possibility of using this strategy in fetuses with congenital abnormalities that require postnatal organ transplantation.…”