CD26 inhibition enhances allogeneic donor-cell homing and engraftment after in utero hematopoietic-cell transplantation
CD26 inhibition enhances allogeneic donor-cell homing and engraftment after in utero hematopoietic-cell transplantation
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DOI：
10.1182/blood-2006-04-018986
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发表时间：
2006-12-15
期刊：
影响因子：
20.3
通讯作者：
Flake, Alan W.
中科院分区：
文献类型：
--
作者：
Peranteau, William H.;Endo, Masayuki;Flake, Alan W.
宫内造血细胞移植（IUHCT）可诱导供者特异性免疫耐受，促进出生后移植。诱导耐受需要混合造血嵌合体的阈值水平。CD26是一种肽酶，其抑制增加出生后移植中造血细胞的归巢和植入。我们假设，CD26抑制将增加供体细胞归巢到胎肝（FL），并改善异基因移植后IUHCT。为了评估这一假设，将B6GFP骨髓（BM）或富集的造血干细胞（HSC）移植到具有或不具有OD 26抑制的同种异体胎鼠中。从4到28周的生活接受者进行了FL归巢和外周血嵌合体分析。我们发现，供体细胞的CD26抑制导致（1）同种异体BM和HSC向FL的归巢增加，（2）具有出生后植入证据的注射动物数量增加，（3）IUHCT后供体嵌合体水平增加，以及（4）与非抑制的同类供体细胞相比具有竞争性植入优势。这项研究支持CD26抑制作为一种潜在的方法，以增加FL归巢和植入后IUHCT的水平。由此产生的供体嵌合性增加表明，CD26抑制可能在未来被用作增加IUHCT后供体特异性耐受性的方法。
In utero hematopoietic-cell transplantation (IUHCT) can induce donor-specific tolerance to facilitate postnatal transplantation. Induction of tolerance requires a threshold level of mixed hematopoietic chimerism. CD26 is a peptidase whose inhibition increases homing and engraftment of hematopoietic cells in postnatal transplantation. We hypothesized that CD26 inhibition would increase donor-cell homing to the fetal liver (FL) and improve allogeneic engraftment following IUHCT. To evaluate this hypothesis, B6GFP bone marrow (BM) or enriched hematopoietic stem cells (HSCs) were transplanted into allogeneic fetal mice with or without OD26 inhibition. Recipients were analyzed for FL homing and peripheral-blood chimerism from 4 to 28 weeks of life. We found that CD26 inhibition of donor cells results in (1) increased homing of allogeneic BM and HSCs to the FL, (2) an increased number of injected animals with evidence of postnatal engraftment, (3) increased donor chimerism levels following IUHCT, and (4) a competitive engraftment advantage over non-inhibited congenic donor cells. This study supports CD26 inhibition as a potential method to increase the level of FL homing and engraftment following IUHCT. The resulting increased donor chimerism suggests that CD26 inhibition may in the future be used as a method of increasing donor-specific tolerance following IUHCT.