For clinical purposes the CD34 surface antigen characterises hematopoietic progenitor or stem cells (HSC) and will be measured routinely for peripheral hematopoietic stem cell transplantation (PBSCT). Concerning homing mechanisms of HSC not only the number of CD34+ cells could be important. However, there are several other characteristic surface antigens indicating proliferation. For example, the cell surface receptor CD184 has been found on CD34+ HSC and seems to be necessary for stem cell development and migration. CD184 knock-out mice are known to present insufficient hemato- and lymphopoiesis. MMP9, a gelatinase cleaving collagen typ IV, expressed on HSC, is necessary for migration and probably also for HSC engraftment. In leukapheresis products used for PBSCT we were interested in CD184 and MMP9 protease expression on CD34+ cells and their impact on homing.
Methods: 84 leukapheresis products for autologous stem cell transplantation were analysed in 65 patients. The patients suffered from oncologic (n= 45) and haematological (n=20) malignancies. There was no bone marrow infiltration found before starting leukapheresis. Expression of CD184 and MMP9 on CD34+ cells were analysed by flow cytometry. Additionally, the number of CD45+ cells was measured (BD Biosciences). Statistical analysis was run by SPSS using students t-test and Mann-Whitney-U test.
Results: 44,7% (+/− 3,1%) of CD34+ cells presented the CD184+ antigen, but MMP9+ expression was found only in 5% (+/− 1,4%) of CD34+ HSC, respectively. Regarding the patients age, sex or underlying diseases no significant differences were seen.
Discussion: High expression rate of CD184 antigen and MMP9 on CD34+ HSC could be favorable for engraftment and success of hematopoietic stem cell transplantation. Surprisingly, in our study on leukapheresis products less than half of CD34+cells were found to express CD184+ antigen, and only 5% presented MMP9 expression. As time to engraftment after PBSCT of the patients did not differ from mean values either antigen expression could develop on a further step of hematopoietic reconstitution or the patients presented an "alternative pathway" establishing hematopoiesis and immune defense mechanisms. Further studies on proliferation and differentiation mechanisms of HSC are requested.
Disclosure:Membership Information: Dr. Wolf: Chugai Pharma Speaker’s Bureau in 2006.