Campbell Timothy B, Hangoc Giao, Liu Ying, Pollok Karen, Broxmeyer Hal E
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA.
Stem Cells Dev. 2007 Jun;16(3):347-54. doi: 10.1089/scd.2007.9995.
CD26, a surface serine dipeptidylpeptidase IV (DPPIV) expressed on different cell types, cleaves the amino-terminal dipeptide from some chemokines, including stromal-derived factor-1 (SDF-1/CXCL12). SDF-1/CXCL12 plays important roles in hematopoietic stem cell (HSC) homing, engraftment, and mobilization. Inhibition of CD26 peptidase activity enhances homing, engraftment, and competitive repopulation in congenic mouse bone marrow cell transplants. Our studies evaluated a role for CD26 in in vivo engraftment of HSCs from human umbilical cord blood (CB) into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Pretreating purified CD34(+) human CB cells with Diprotin A, a DPPIV inhibitor, for 15 min significantly enhanced engraftment. Treatment did not affect differentiation of CD34(+) cells in vivo, as measured phenotypically by human markers CD33, CD38, CD19, and CD34. We found that the percentage of CD26(+) cells within the more immature cells (CD34(+)CD38()) was significantly higher than in the more mature population (CD34(+)CD38(+)). These results suggest that inhibition of CD26 may be one way to enhance engraftment of limiting numbers of stem cells during CB transplantation.
CD26是一种在不同细胞类型上表达的表面丝氨酸二肽基肽酶IV（DPPIV），可从包括基质衍生因子-1（SDF-1/CXCL12）在内的一些趋化因子上切割氨基末端二肽。SDF-1/CXCL12在造血干细胞（HSC）归巢、植入和动员中发挥重要作用。抑制CD26肽酶活性可增强同基因小鼠骨髓细胞移植中的归巢、植入和竞争性再增殖。我们的研究评估了CD26在人脐带血（CB）来源的HSC体内植入非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠中的作用。用DPPIV抑制剂二肽基肽酶抑制剂A预处理纯化的CD34(+)人CB细胞15分钟可显著增强植入。如通过人标志物CD33、CD38、CD19和CD34进行表型测量，该处理不影响CD34(+)细胞在体内的分化。我们发现，在更不成熟的细胞（CD34(+)CD38(−)）中，CD26(+)细胞的百分比显著高于更成熟的群体（CD34(+)CD38(+)）。这些结果表明，抑制CD26可能是增强CB移植过程中有限数量干细胞植入的一种方法。
