Regulation of immunological balance between TH1/TH2 and Tc1/Tc2 lymphocytes by prostaglandin E2 / 中国实验血液学杂志

This study was purposed to investigate the effect of prostaglandin E2 (PGE2) on proliferation of peripheral blood T lymphocytes, and to evaluate the regulatory role of PGE2 on immunological balance between Th1/Th2 and Tc1/Tc2 lymphocytes. The peripheral blood mononuclear cells (PBMNC) were stimulated by anti-human CD3 monoclonal antibody (mAb) and anti-human CD28 mAb, and were cultured in the presence of different concentration of PGE2 for 120 hours. The proliferation of peripheral blood T lymphocytes was assayed according to the manufacture protocol of BrdU Kit; the IFN-gamma and IL-4 levels in supernatants cultured for 24, 48, 72 and 120 hours were detected by ELISA; the ratios of CD4+IL-4+ T cells/CD4+ IFN-gamma+ T cells and CD8+IL-4+ T cell/CD8+IFN-gamma+ T cells were determined by flow cytometry. The cells cultured without PGE2 were used as control. The results indicated that (1) with the raising of concentration of PGE2, the inhibitory rate of T cell proliferation in vitro significantly increased (p=0.001). There was significant positive correlation between inhibitory rate of T cells and PGE2 concentration (correlation coefficient=0.889, p=0.000). (2) the difference between the IFN-gamma concentrations in supernatant cultured for 120 and 72 hours in test groups had no statistical significance (p=0.917). The IFN-gamma concentration increased continually with prolonging of culture time in control group (p=0.046). The IFN-gamma concentrations produced at different times in test group were significantly lower compared with those in control group (p<0.05). The IL-4 concentrations produced at different time had no significant change in test groups (p=0.400). The IL-4 concentration in 24 hours in control group was significantly higher than that at 48, 72 and 120 hours in control group (p=0.007, 0.003 and 0.002). After cultured for 24 hours the IL-4 concentration in test group was significantly lower than that in control group (p=0.037), but after cultured for 48, 72 and 120 hours, the IL-4 concentration in test group did not show statistical difference in comparison with control group (p>0.05). (3) the proportions of CD4+IFN-gamma+T cells in test group and in control group had no significant difference (p=0.767). The proportion of CD4+IL-4+T cells in test group was slightly higher than that in control group (p=0.051). The ratio of CD4+IL-4+T cells to CD4+IFN-gamma+ T cells in test group was significantly higher than that in control group (p=0.011). The proportions of CD8+IFN-gamma+ T cells in test group and in control group had no statistical difference (p=0.441). The proportion of CD8+IL-4+T cells in test group was significantly higher than that in control group (p=0.015). The ratio of CD8+IL-4+ T cells to CD8+IFN-gamma+ T cells in test group were obviously higher than that in control group(p=0.038). It is concluded that the PGE2 inhibits the proliferation of T lymphocytes in vitro. PGE2 influences the production of IFN-gamma and IL-4, and significantly influences peak appearance of IFN-gamma produced by T lymphocyte. PGE2 can continuously inhibit the production of IFN-gamma, but its continuous effect on IL-4 is no significant. PGE2 enhances the ratio of CD4+IL-4+T lymphocytes to CD4+IFN-gamma+T lymphocytes and the ratio of CD8+IL-4+T lymphocytes to CD8+IFN-gamma+T lymphocytes, and regulates development of T cells toward Th2/Tc2 cells.

Ameliorative effect of rat bone marrow mesenchymal stem cell transplantation on infracted heart function / 中国实验血液学杂志

This study was purposed to investigate the effects of rat marrow mesenchymal stem cell (rMSC) transplantation on left ventricular (LV) function in a rat myocardial infarction model. Myocardial infarction was performed in male Lewis rats by ligating the proximal left coronary artery. Rats were randomly divided into 3 groups: sham operation group (only thoracotomy, n = 8), AMI group (DF12 injection, n = 10), rMSC group (Dil-Labeled rMSC transplantation). At 8 weeks later, the cardiac functions including left ventricular ejection fraction (LVEF), left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), +dp/dtmax and -dp/dtmax were evaluated by echocardiography and cardiac catheterization. The presence and differentiation of engrafted cells were assessed. CD31 was detected by immunohistochemical staining to demonstrate neovascular formation. The results indicated that the cultured in vitro rMSC expressed CD90, CD44, CD105, CD54; did not express CD34, CD45, CD31, as compared with AMI group, rMSC group showed a significant increase of LVEF, LVESP, +dp/dtmax, -dp/dtmax and a significant decrease of LVEDP. Immunofluorescence demonstrated that some transplanted rMSCs were positive for myosin, suggesting that small number of transplanted rMSCs differentiated into cardiac-like cells. Immunostaining showed marked augmentation of capillary density in the rMSC group than that of AMI group. It is concluded that transplanted rMSCs can differentiate into cardiac-like cells and rMSC transplantation can improve LV function after myocardial infarction in rats.

Invasive fungal infections after allogeneic hematopoietic stem cell transplantation and related risk factors / 中国实验血液学杂志

In order to analyze the incidence and high-risk factors of invasive fungal infections among recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), 180 cases of allo-HSCT were enrolled in this study. The incidence and risk factors of IFI were analyzed by method of Kaplan-Meier and Cox regression model. The results showed that an incidence of IFI in 35 cases (19.5%) were detected, with 1 case proven and 34 cases probably diagnosed, which was composed of 18 cases (51.4%) of aspergillosis and 17 cases (48.6%) of candidosis. There was significant difference in one-year overall survival rate between patients with (34.3%) or without (53.8%) IFI. In univariate analysis, risk factors of IFI included: pretransplant fungal infection or colonization, unrelated donor (peripheral blood or bone marrow stem cell) transplantation, acute GVHD, extensive chronic GVHD and the use of methylprednisolone. In multi-variate analysis, the following risk factors of IFI were found:unrelated donor for allogeneic peripheral blood or bone marrow stem cell transplantation, acute GVHD and pretransplant fungal infection or colonization acute GVHD (RR: 2.399, 1.589, and 0.836). It is concluded that IFI is a frequent complication and one of the leading causes of mortality among recipients of allo-HSCT. As for patients with higher risk of IFI, early interventions should be taken.

Differentiation of bone marrow derived from mesenchymal stem cells into cardiomyocyte-like cells induced by co-culture with rat myocardial cells / 中国实验血液学杂志

The study was purposed to investigate the differentiation ability of mesenchymal stem cells (MSCs) into myocardial cells in vitro. Rat bone marrow-derived MSCs were labeled and co-cultured with neonatal rat cardiomyocytes (CM) for 5 - 7 days. The expression of cell surface antigens was detected by flow cytometry, and the expression of muscle-specific marker myosin and troponin T in labeled cells was detected by immunofluorescence. The results showed that in vitro cultured MSCs expressed CD90, CD44, CD105, CD54, not expressed CD34, CD45, CD31. After co-cultured with neonatal rat CM, labeled MSCs differentiated into cardiomyocyte-like cells expressing myosin and troponin T. It is concluded that MSCs can differentiate into cardiomyocyte-like cells when co-cultured with neonatal myocardial cells in vitro. In co-culture of two kind of cells in ratio of four to one showed obvious efficacy differentiating MSCs into CMs.

Comparative analysis between autologous and allogeneic hematopoietic stem cell transplantation in 114 adult patients with acute lymphoblastic leukemia in long-term follow-up / 中国实验血液学杂志

This study was aimed to explore the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients with acute lymphoblastic leukemia and to analyze the related prognostic factors. Clinical data of 114 ALL patients receiving HSCT, including 70 auto-HSCT and 44 allo-HSCT, were retrospectively analyzed. Disease-free-survival (DFS), relapse-rate (RR) and transplantation-related-mortality (TRM) of patients receiving different HSCT were compared. The results showed that the eight-year OS and DFS in a total of 114 adult ALL patients were (40.89+/-5.27)% and (39.50+/-5.22)% respectively. The three-year DFS of ALL patients who received HSCT in phase CR1 and no CR1 were (47.63+/-5.63)% and (17.65+/-9.25)% (p=0.0034). The two-year DFS of patients who received allo-HSCT and had I/II aGVHD was (62.75+/-12.30)%, and the six-month DFS of patients who had III/IV aGVHD was 0, and the two-year DFS of patients without aGVHD was (29.35+/-9.70)% (p=0.005). The three-year DFS of patients with and without maintenance chemotherapy after transplantation were (55.12+/-7.89)% and (33.33+/-11.11)% respectively, there was significant difference between them (p=0.0499). The five-year DFS between patients received auto-HSCT and allo-HSCT in phase CR1 was not significantly different. The RR of patients received allo-HSCT was lower than that of patients received auto-HSCT, but there was no significant difference between them. The TRM of patients received allo-HSCT was higher than of patients received auto-HSCT (p=0.0313). Expression of myeloid antigen and higher LDH level in diagnosis were poor- prognostic factors. It is concluded that auto-HSCT and allo-HSCT completed in phase CR1 may improve prognosis of the patient with ALL as a method for consolidation chemotherapy, but no significant difference exists between the two HSCTs. Patients receiving allo-HSCT and having I/II aGVHD may achieve higher DFS. The maintaining chemotherapy for patients after auto-HSCT may improve therapeutic effect.

Clinical study on acute kidney injury after myeloablative allogeneic hematopoietic cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the incidence, pathogenesis, risk factors, prophylaxis and treatment of acute kidney injury (AKI) after myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Clinical data of 120 patients received myeloablative allo-HSCT were retrospectively analyzed.</p><p><b>RESULTS</b>Serum creatinine level in the patients showed significantly higher than baseline value at 28-60 days after transplantation (P<0.05). 73 patients (60.8%) developed AKI at a median of 33 days after allo-HSCT, including grade 2 in 32 patients (26.7%). Patients with grade 1 AKI showed significant higher serum cyclosporine A (CsA) levels (P<0.05). Hepatic veno-occlusive disease( HVOD), acute graft-versus-host disease (aGVHD) and total bilirubin > 40 micromol/L were high risk factors of occurring AKI (P<0.05). 19 patients died within 100 days after allo-HSCT, grade 2 AKI was a high risk factor of mortality (P< 0.05). 180-day survival rate was significantly lower in patients with grade 2 AKI after allo-HSCT (P<0.05).</p><p><b>CONCLUSION</b>AKI is one of the major complications after myeloablative allo-HSCT. Prophylaxis and treatment of AKI might reduce mortality in early stage of transplantation.</p>