Peranteau William H, Endo Masayuki, Adibe Obinna O, Merchant Aziz, Zoltick Philip W, Flake Alan W
The Center for Fetal Research, Children's Hospital of Philadelphia, Abramson Research Bldg, Rm 1116B, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, USA.
Blood. 2006 Dec 15;108(13):4268-74. doi: 10.1182/blood-2006-04-018986. Epub 2006 Sep 5.
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 CD26 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 noninhibited 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.
子宫内造血细胞移植（IUHCT）可诱导供体特异性耐受，以促进出生后移植。耐受的诱导需要达到一定阈值水平的混合造血嵌合体。CD26是一种肽酶，其抑制作用可增加出生后移植中造血细胞的归巢和植入。我们推测，抑制CD26会增加供体细胞向胎肝（FL）的归巢，并改善IUHCT后的异基因植入。为了验证这一假设，将B6GFP骨髓（BM）或富集的造血干细胞（HSCs）移植到有或没有CD26抑制的同种异体胎鼠体内。对受体从出生后4周到28周进行胎肝归巢和外周血嵌合体分析。我们发现，对供体细胞进行CD26抑制会导致：（1）同种异体BM和HSCs向FL的归巢增加；（2）有出生后植入证据的注射动物数量增加；（3）IUHCT后供体嵌合体水平提高；（4）相对于未抑制的同基因供体细胞具有竞争性植入优势。本研究支持将抑制CD26作为一种可能的方法，以提高IUHCT后FL归巢和植入的水平。由此增加的供体嵌合体表明，未来抑制CD26可能会被用作一种提高IUHCT后供体特异性耐受的方法。
