PGE2受体特异性激动剂作为促进人造血干细胞归巢与增殖靶向药物的研究

促进供者造血干细胞归巢与增殖是防止移植后植入失败的关键措施之一。近年来国外多个研究均证实了前列腺素E2(PGE2)体外可促进人CD34+细胞归巢与增殖。但人CD34+细胞能同时表达4个PGE2亚受体(EP1～EP4)，PGE2究竟通过其中的哪个亚受体起作用还不清楚。近期我们在国内外首次选用这四个亚受体的特异激动剂(EPA)作为研究对象，初步发现EP2A和EP4A在体外可促进人CD34+细胞的增殖。本课题在此基础上，拟以EP1A和EP3A作为对照，详细探讨EP2A和EP4A体外对人的CD34+ 细胞增殖的影响并比较两者影响的效果，进而从中筛选出一个特异性好、作用强的目标EPxA,然后进一步明确其对CD34+ 细胞归巢与增殖的作用机制。这一研究不仅有助于进一步明确PGE2促进人CD34+细胞归巢与增殖的膜外受体途径，更为重要的是为EPxA在将来有可能成为防止植入失败的特异靶向药物提供依据。

To promote donor haematopoietic stem cells(HSCs) homing and proliferation is one of the crucial measures to prevent graft failure after allo-geneic HSCs transplantation. Recently, some foreign researchers have demonstrated in vitro that prostaglandinE2(PGE2) can not only promotes human CD34+cells homing, but also induces its proliferation.However,it is unknown which subtype receptor is activated eventually by PGE2 since four E-series prostaglandin receptors(EP1～EP4),PGE2 subtype receptors, have been found expressed on the membrane of human CD34+cells. Using the special EP receptor agonists(EPAs) as objects, we recently have found EPA2 and EPA4 could promote CD34+ cells colony formation in vivo.Based on above, taking EP1A and EP3A as control, we are planning to confirm that EP2A AND EP4A could promote human CD34+cells proliferation and homing, and to distinguish their effects. Next,we will screen a more specific and more effective target medicine EPxA, and then desmostrate its mechanism. This study will help us further understand theoretically the extracellular signal pathway promoting human CD34+cells homing and proliferation mediated by PGE2. More importantly, it will provide an evidence to develop EPAx as a new specific target medicine to prevent human CD34+cells graft failure in the future.