OBJECTIVE: To detect the expression level of HK2 gene in the bone marrow of newly diagnosed patients with acute myeloid leukemia (AML) and investigate its influence on the clinical characteristics and prognosis. METHODS: The expression level of HK2 gene in the bone marrow of 90 newly diagnosed patients with AML that accompanying clinical characteristics and survival status were detected by RT-qPCR, and compared with 18 allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors. The Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards regression model were used to analyze the correlation of HK2 expression level with clinical characteristics and prognosis. RESULTS: Compared with allo-HSCT donors, the HK2 expression was significantly increased in newly diagnosed AML patients (P <0.01). Compared with patients with total response (OR, complete response + complete response with incomplete hematologic recovery) after 2 courses of induction chemotherapy, the expression of HK2 in patients without OR was significantly increased (P <0.05). There was a significant difference in the relative expression of HK2 between patients with and without OR after 2 courses of induction therapy (P <0.001). The median survival time of patients with high expression of HK2 was significantly shorter than that of patients with low expression of HK2 (P <0.05). The multivariate Cox proportional hazards regression analysis showed that prognostic stratification, the expression level of HK2, and whether two courses of induction therapy achieved OR were independent factors affecting the prognosis of AML patients (P <0.05). CONCLUSIONS Compared with allo-HSCT donors, the expression level of HK2 gene is increased in the bone marrow of newly diagnosed AML patients. The prognosis of patients with high expression of HK2 is poor. The expression level of HK2 is an independent factor affecting the prognosis of AML patients.
Humans ; Bone Marrow ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

No abstract available.
Adult ; Bone Marrow/*pathology ; Fatal Outcome ; Graft vs Host Disease/etiology ; High-Throughput Nucleotide Sequencing ; Humans ; Liver Cirrhosis/pathology/*therapy ; *Liver Transplantation/adverse effects ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction ; *Polymorphism, Single Nucleotide ; Transplantation Chimera/*genetics

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1x10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.
Bone Marrow ; Drug-Related Side Effects and Adverse Reactions ; Graft vs Host Disease* ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stromal Cells* ; Myalgia ; Population Characteristics

OBJECTIVE: To observe the repairing effects of bone marrow transplantation with nerve tissue committed stem cell (NTCSCs) on experimental rats with injury of noise-induced hearing loss. METHOD: Guinea pigs were randomly divided into control group, noise exposure group and the transplanting group. A week after white noise exposure of 110 dB, NTCSCs and PBS were injected into guinea pigs of the noise exposure group and the transplanting group respectively. One week after noise exposure to four weeks continuous administration. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise,1, 2 and 4 weeks post-drugs, The changes of cochlea hair cells were also observed by a scan electron microscope (SEM). RESULT: The ABR threshold shifts in the transplanting group were significantly fewer than that in the noise exposure group. SEM showed that hear hair of the inner and outer hair cells in noise exposure group displayed mess, fusion and imperfections. In the transplanting treatment group, the hair cells displayed slight pathological changes, there wasn't significant differents comparied with normal group. The number of OHCs were relatively stable in the normal group, while the obvious OHC loss was observed in other groups. There was significant difference among the three groups, however, the OHC loss in the transplanting group was no significantly different to that in the noise exposure (P > 0.05). CONCLUSION The bone marrow NTCSCs which had been transplanted to rat cochlea could reduce the damage of the noise on the hair cell, and thus played a role in repairing the damage of auditory nerve.
Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Cochlea ; Guinea Pigs ; Hair Cells, Auditory, Outer ; pathology ; ultrastructure ; Hearing Loss, Noise-Induced ; therapy ; Noise ; adverse effects ; Rats ; Stem Cell Transplantation

BACKGROUNDThe effects of donor characteristics on CD34(+) cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) were used. The aim of this study was to investigate the effects of donor characteristics on CD34(+) cell dose in mixture allografts of G-BM and G-PB.

METHODSA total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People's Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 µg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34(+) cell dose less than 2×10(6) cells/kg recipient body weight was considered a poor mobilization.

RESULTSOf the 162 donors, 31 (19.1%) did not attain this threshold. The obtained median CD34(+) cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×10(6)/kg, 2.40×10(6)/kg, and 3.47×10(6)/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34(+) cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index (BMI), and weight.

CONCLUSIONDonor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34(+) cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34(+) cells for transplantation.

Adolescent ; Adult ; Aged ; Allografts ; Antigens, CD34 ; metabolism ; Bone Marrow ; Bone Marrow Transplantation ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; metabolism ; Hematopoietic Stem Cell Mobilization ; adverse effects ; Humans ; Male ; Middle Aged ; Prospective Studies ; Tissue Donors ; Young Adult

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%+/-8.5% vs 1.6%+/-7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)
Adult ; Aged ; Bone Marrow Cells/cytology ; Cell- and Tissue-Based Therapy/*adverse effects ; Echocardiography ; Female ; Heart/physiopathology ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/*adverse effects ; Mesenchymal Stromal Cells/*cytology ; Middle Aged ; Myocardial Infarction/*therapy ; Pilot Projects ; Stroke Volume ; Tomography, Emission-Computed, Single-Photon ; Transplantation, Autologous ; Treatment Outcome ; Ventricular Function, Left ; Young Adult

This study was aimed to investigate the effect of PTD-mFoxp3 fusion protein on graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. The 10-weeks-old C57BL/6 mice as recipients were randomly divided into three groups (A,B and C), 10 mice were in each group. The mice on day of transplantation as on day 0 received total body irradiation (TBI) 6.0 Gy, then the bone marrow cells (BMC) from BALB/c mice were injected through tail vein within 4-6 hours. At 2 days before transplantation and 0, 1, 3, 5, 7, 9 and 13 days after transplantation, mice in group A were injected with saline, mice in group B were injected with mFoxp3 protein and mice in group C were injected with PTD-mFoxp3 fusion protein. Symptoms of GVHD, survival time and histopathological changes were observed. The establishment of mixed chimerism was determined by flow cytometry in day 60, and IL-2 and IFN-γ expression profiles in the recipient peripheral blood were assessed by ELISA. The results showed that the mean survival time of recipients in group A,B and C was (32.95 ± 5.48) , (38.00 ± 5.45) and (55.30 ± 3.15) respectively. Graft rejection was observed in the liver and small intestine specimens of group A and group B. The serum levels of IL-2 and IFN-γ significantly decreased in the recipients of group C, as compared with the other groups. The flow cytometry analysis revealed that the survival recipient mice developed high chimerism levels, the percentages of donor cells in group A,B and C were (79.46 ± 1.80) %, (79.13 ± 2.23) % and (85.92 ± 2.82) % respectively. It is concluded that PTD-mFoxp3 fusion protein can reduce the incidence and mortality of GVHD after allogeneic bone marrow transplantation.
Animals ; Bone Marrow Transplantation ; adverse effects ; Female ; Forkhead Transcription Factors ; therapeutic use ; Graft vs Host Disease ; metabolism ; therapy ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Recombinant Fusion Proteins ; therapeutic use ; Transplantation, Homologous

This study was purposed to explore the cellular source of IL-22 in graft versus host disease (GVHD) mouse following allo-genetic bone marrow transplantation. BALB/c and C57BL/6 mice were used as recipients and donors, respectively. GVHD model was established by irradiated BABL/c mice inoculated with mixed suspension of C57BL/6 bone marrow cells and splenic lymphocytes. The mice were divided into normal group (normal), total body irradiated group (TBI), bone marrow cell-transplanted group (BMT), and the combination of bone marrow cell and splenic lymphocytes-induced GVHD group (BS). The level of IL-22 in plasma was detected by ELISA. The cellular source of IL-22 and IL-22(+) subsets were detected by flow cytometry. The results showed that compared with normal mice, the level of IL-22 in plasma from BS mice was the highest (P < 0.01). All the lymphocytes of spleen, lymph nodes and peripheral blood from BS mice could produce IL-22, in which the percentage of IL-22(+)CD4(+) T cell was higher than that of IL-22(+)CD8(+) T cells. Not only Th22 cells but also Th1 and Th17 cells were the cellular source of IL-22 in GVHD mice. It is concluded that the high level of IL-22 has been found in mice with GVHD, which mainly originates from IFN-γ(-)IL-17(-)IL-22(+) Th22 cells.
Animals ; Bone Marrow Transplantation ; adverse effects ; methods ; Female ; Graft vs Host Disease ; blood ; Interleukins ; blood ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous

Bone Marrow Transplantation ; adverse effects ; Humans ; Pneumonia ; diagnosis

OBJECTIVETo investigate the effects of immature dendritic cells (imDC) expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD) in allogeneic bone marrow transposed (allo-BMT) mouse model.

METHODSWe constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC effectively in vitro. GVHD model was established with C57BL/6(H-2b) donor mice and BALB/c (H-2d) recipient mice. After irradiation, recipients were injected with donor bone marrow and spleen cells along with CCR7-modified dendritic cells. Mice were randomized into irradiation, transplant control, pXZ9-imDC (empty vector control) and CCR7-imDC groups. Survival, GVHD score, histopathological analysis and plasma levels of inflammatory cytokines were observed.

RESULTSThe mean survival in irradiation, transplantation, pXZ9-imDC and CCR7-imDC groups were (8.20±1.48)d, (12.20±2.78)d, (20.70±6.01)d and (27.5±7.55)d respectively. The survival in CCR7- imDC group was significantly improved compared with other groups (P<0.05). GVHD scores in transplantation, pXZ9-imDC and CCR7-imDC groups were (6.90±1.66), (5.60±0.97) and (4.10±1.79) respectively. CCR7-imDC group had significantly lower GVHD score and minor tissue damages shown by histopathological analysis than the other groups. Plasma IFN-γ level increased and reached the peak at +10 day in transplant group, while it gradually decreased in pXZ9-imDC and CCR7-imDC groups, and then reached the nadir at +20 day post-allo-BMT, with the lowest level in CCR7-imDC group (P<0.01). Plasma IL-4 decreased in transplant group, while it gradually increased in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in CCR7- imDC group (P<0.01). The 95%-100% of H-2b positive cells in recipient mice on + 30 day post-allo-BMT demonstrated the complete donor- type implantation.

CONCLUSIONGenetically modified immature DC by CCR7 gene could alleviate damages by GVHD and prolong survival of recipient mice after allo-BMT.

Animals ; Bone Marrow Transplantation ; adverse effects ; Dendritic Cells ; cytology ; Genetic Vectors ; Graft vs Host Disease ; prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, CCR7 ; genetics ; Transplantation, Homologous