ABSTRACT
Objective To investigate the role of stromal cell-derived factor-1α(SDF-1α)/CXCR4 signal pathway in the therapeutic effects of hypoxic preconditioning endothelial progenitor cell (HEPC) transplantation on acute myocardial in-farction Methods Bone marrow endothelial progenitor cells (EPCs) were isolated from syngeneic adult male Wistar rats. EPCs were cultured under normoxic condition for 4 days and 1%O2+5%CO2+94%N2 condition for 3 days. The effect of HEP-Cs on the migration ability of 100μg/L SDF-1αwas observed. Western blot assay was used to detect the expression of CX-CR4, the solo receptor of SDF-1α on cells surface. Then, 26 syngeneic adult male Wistar rats were randomized into 3 groups:control group (n=8),EPCs group (n=9) and HEPCs group (n=9). The acute myocardium infarction animal model was established. At infarction, the rats received 5-points peri-infarct intramyocardial injections of PBS 200μL, 2×106 EPCs and 2 × 106 HEPCs. After 4 weeks, the haemodynamics parameters of cardiac function were analyzed by echocardiography. Results Compare with EPCs, the migration ability of HEPCs towards SDF-1α was increased significantly. The result of Western blot analysis showed an increased CXCR4 expression on the cell surface. After 4 weeks of transplantation, the left ventricular end systolic diameter and ejection fraction (EF%) were much improved in HEPCs group than those of EPCs group and control group (P＜0.05). Compare with control group, the left ventricular end-diastolic diameter was significantly im-proved in EPCs and HEPCs groups (P＜0.05). There was no significant difference in the improvement of the left ventricular end-diastolic diameter between HEPCs and EPCs groups (P>0.05). Conclusion SDF-1α/CXCR4 pathway was up-regu-lated by HEPCs, which showed the therapeutic effects via EPCs. The adjustment of SDF-1α/CXCR4 signaling pathway is an effective method for the treatment of ischemic heart diseases.
ABSTRACT
BACKGROUND: Rapid platelet engraftment has several economic benefits by reducing the cost of supportive therapy as well as reducing the risk of fatal bleeding due to severe thrombocytopenia. Based on these considerations, we genotyped human platelet alloantigens (HPA) to evaluate the effect of minor transplantation antigen mismatches on the rate and speed of platelet recovery and clinical outcome of transplantation. METHODS: Thirty-five patients with various hematologic diseases transplanted between January 2001 and August 2004 were included. Genomic DNA was isolated from peripheral blood of donor-recipient pairs before transplantation. HPA-1, -2, -3, -4, -5, and -6 genotyping was performed by poly-merase chain reaction (PCR)-sequence specific primers (SSP). The effects of HPA compatibility on platelet recovery, incidences of graft-versus-host disease (GVHD) and relapse, and overall survival was investigated. RESULTS: There were no significant differences in platelet recovery according to HPA matching status. We observed no statistically significant differences in the occurrence of relapse and overall survival according to HPA-1, -2, and -3 matched/mismatched groups of patients, whereas HPA-3 mismatching was found to have a significant effect on GVHD development. There was also no difference in GVHD occurrence according to HPA-1 and -2 matched or mismatched transplants. CONCLUSIONS: Since platelet recovery in the HPA-1, -2, -3, and -5 matched/mismatched groups is not significantly different, the seems that platelet glycoprotein (GP) does not seem to act as a factor influencing the homing of hematopoietic stem cells. The finding that HPA-3 incompatibility may be involved in GVHD can be of importance. If a role for HPA-3 as minor histocompatibility antigens is confirmed by additional studies, we can ameliorate the outcome of allogeneic stem cell transplantation by typing of HPA and selecting the most closely related donors.