Inhibition of CD26 in human cord blood CD34+ cells enhances their engraftment of nonobese diabetic/severe combined immunodeficiency mice
Inhibition of CD26 in human cord blood CD34+ cells enhances their engraftment of nonobese diabetic/severe combined immunodeficiency mice
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DOI：
10.1089/scd.2007.9995
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发表时间：
2007-06-01
影响因子：
4
通讯作者：
Broxmeyer, Hal E.
中科院分区：
文献类型：
--
作者：
Campbell, Timothy B.;Hangoc, Giao;Broxmeyer, Hal E.
CD26是一种表达于不同细胞类型的表面丝氨酸二肽基肽酶IV(DPPIV)，可从包括基质衍生因子-1(SDF1/CXCL12)在内的一些趋化因子中裂解氨基末端二肽。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多肽酶活性可增强同源小鼠骨髓细胞移植的归巢、植入和竞争性再繁殖。我们的研究评估了CD26在体内从人脐血(CB)中移植到非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠体内的作用。用DPPIV抑制剂Diprotin A处理CD34(+)人脐血细胞15min，可显著提高其植入能力。根据人类标志物CD33、CD38、CD19和CD34的表型，治疗不影响体内CD34(+)细胞的分化。我们发现CD26(+)细胞在较不成熟的细胞(CD34(+)、CD38(-))中的百分比明显高于较成熟的人群(CD34(+)、CD38(+))。这些结果表明，抑制CD26可能是在脐带血移植过程中增强有限数量干细胞植入的一种方式。
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 (SDF1/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.