The maternal immune response inhibits the success of in utero hematopoietic cell transplantation.
The maternal immune response inhibits the success of in utero hematopoietic cell transplantation.
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DOI：
10.4161/chim.2.2.16287
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Mackenzie, Tippi C
中科院分区：
文献类型：
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作者：
Nijagal, Amar;Wegorzewska, Marta;Mackenzie, Tippi C
子宫内造血细胞移植（IUHCTx）是治疗先天性干细胞疾病的一种有前途的策略。尽管据称胎儿免疫系统不成熟，但这种策略的临床成功受到移植细胞植入不良的限制。胎儿宿主免疫系统被认为是实现成功IUHCTx的主要障碍。然而，由于胎儿的免疫系统是不成熟的，我们假设母体的免疫反应可能是IUHCTx的真正屏障。我们已经证明，母体T细胞运输到胎儿后，同种异体在子宫内移植，这些淋巴细胞在限制植入发挥关键作用。此外，我们已经表明，MHC匹配供体细胞的母亲提高了在不匹配的胎儿植入。这些结果有助于重新关注利用胎儿环境治疗先天性干细胞疾病患者。
In utero hematopoietic cell transplantation (IUHCTx) is a promising strategy for the treatment of congenital stem cell disorders. Despite the purported immaturity of the fetal immune system, the clinical success of this strategy has been limited by poor engraftment of transplanted cells. The fetal host immune system is thought to be the major barrier to achieving successful IUHCTx. Since the fetal immune system is immature, however, we hypothesized that the maternal immune response may instead pose the true barrier to IUHCTx. We have demonstrated that maternal T cells traffic into the fetus after allogeneic in utero transplantation and that these lymphocytes play a critical role in limiting engraftment. Furthermore, we have shown that MHC matching the donor cells to the mother improves engraftment in the unmatched fetus. These results help renew interest in using the fetal environment to treat patients with congenital stem cell disorders.