A preliminary analysis of the balance between Th1 and Th2 cells after CD34+ cell-selected autologous PBSC transplantation

BACKGROUND: CD34+ cell-selected autologous PBSC transplantation (CD34+ APBSCT) is a procedure used for the treatment of patients with malignant disease that is intended to eliminate residual tumor cells from autologous grafts. However, frequent infectious complications after CD34+ APBSCT can occur. A delay of recovery of the absolute number of CD4+ T cells after transplantation was reported to be one disadvantageous factor. As data on T-cell function after CD34+ APBSCT are scanty, we analyzed changes in T-helper cell 1 (Th1) and T-helper cell 2 (Th2) after CD34+ APBSCT to evaluate immune reconstitution. METHODS: Twelve patients underwent APBSCT (CD34+APBSCT group, n=4, and unselected APBSCT, n=8). Peripheral blood (PB) samples were obtained at 2, 4, 8, 12 and 16 weeks after the transplantation. The dynamics of the Th1 and Th2 were analyzed at a single-cell level, using flow cytometry. RESULTS: In the CD34+ APBSCT group, not only the absolute count of CD4+ T cells but also the proportion of Th1 cells in CD4+ T cells and the ratio of Th1 to Th2 after transplantation were significantly decreased at 2 and 4 weeks after transplantation compared with findings in the unselected APBSCT group. DISCUSSION: We suggest that higher rates of infectious complications after CD34+ APBSCT may be due to the inability of residual T cells from the CD34+ cell selection to generate mature T cells that function adequately against infection. Although further study would be required, our preliminary data provide some information on the immune reconstitution after CD34+ APBSCT and differentiation of T lymphocytes into Th1 and Th2 in vivo.     

Intermediate-dose CY and G-CSF more efficiently mobilize adequate numbers of PBSC for tandem autologous PBSC transplantation compared with low-dose CY in patients with multiple myeloma

BACKGROUND: Autologous PBSC transplantation is the standard care for patients with multiple myeloma. The most common regimen used to mobilize PBSC consists of CY and G-CSF. METHODS: We retrospectively analyzed the efficacy and toxicity of two regimens of CY for PBSC mobilization: low-dose CY (1-2 g/m(2), LD-CY, n=61) plus G-CSF, and intermediate-dose CY (3-4 g/m(2), ID-CY, n=26) plus G-CSF. RESULTS: In the LD-CY group, 5.17 (0.23-17.3)x10(6) CD34(+) cells/kg, and in the ID-CY group 7.71 (0.08-26.4)x10(6) CD34(+) cells/kg (P=0.018), were collected. Although >/=2x10(6)/kg CD34(+) cells were collected in 89% of the LD-CY group and 92% of the ID-CY group, this was achieved after a single leukapheresis in 54% of the LD-CY group and 92% of the ID-CY group (P=0.0001). Patients who are to have tandem autologous PBSC transplants require >/=4x10(6)/kg CD34(+) cells. This was achieved in only 65% patients in the LD-CY group but 88% in the ID-CY group (P=0.05). Among patients who had not had prior melphalan and/or >12 months of prior treatment, 74% in the LD-CY group and 100% in ID-CY group mobilized >/=4x10(6)/kg CD34(+) cells. Febrile neutropenia was more frequent in the ID-CY group (38% vs. 13%). DISCUSSION: In conclusion, compared with LD-CY, patients receiving ID-CY were more likely to collect a total CD34(+) cell number adequate for tandem autologous PBSC transplantation. The increased toxicity was manageable and considered acceptable.     

Study of the impact of intramyocardial implantation of stem cells on myocardial perfusion and contractility in patients with coronary heart disease concurrent with postinfarct cardiosclerosis and chronic heart failure

OBJECTIVE: to study of intramyocardial implantation of cultured bone marrow stem cells on myocardial perfusion and contractility in the surgical treatment of patients with coronary heart disease (CHD) and chronic heart failure (CHF), by synchronized single-photon emission computed tomography (SSPECT) of the myocardium. SUBJECTS AND METHODS: The study included 11 patients. Intramyocardial injection of cell injections into the myocardial periscarring areas was made at coronary bypass surgery. All the patients underwent 99mTc myocardial SSPECT MIBI before and 3, 6, 12 months after surgery. RESULTS AND CONCLUSIONS: Implantation of bone marrow stem cells into the left ventricular myocardium favorably affects left ventricular remodeling and contributes to the improvement of myocardial perfusion and contractility, as evidenced by 99mTc.     

Morphological changes after large-field irradiation of dogs and autologous bone marrow transplantation

The effect of an automyelotransplant taken from a nonirradiated area of bone marrow has been studied after large fields irradiation in dogs. Certain changes occurring in the hemopoietic organs and in some other vitally important organs have been revealed. The automyelotransplantation contributes to a quicker repopulation of the bone marrow and stimulates lymphoid hemopoiesis in the spleen; that plays a positive role in overcoming the bone marrow syndrome at radiation illness. In other organs (gastrointestinal tract, kidneys, lungs, heart) given various doses of irradiation, in the control and test (with automyelotransplantation) groups similar morphological changes have been revealed.     

Serum after autologous transplantation stimulates proliferation and expansion of human hematopoietic progenitor cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34(+) cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34(+), CD133(+), CD45(-)) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool.     

Timing of transplantation of autologous bone marrow derived mesenchymal stem cells for treating myocardial infarction

It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction.The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion.However,the adverse inflammatory environment,with its high oxidative stress,might be deleterious if cells are administered too early after reperfusion.Here we highlight several aspects of the timing of intracoronary stem cell therapy.Our results showed that transplantation of bone marrow mesenchymal stem cells at 2 4 weeks after myocardial infarction is more favorable for reduction of the scar area,inhibition of left ventricular remodeling,and recovery of heart function.Coronary injection of autologous bone marrow mesenchymal stem cells at 2 4 weeks after acute myocardial infarction is safe and does not increase the incidence of complications.     

自体骨髓间充质干细胞移植治疗难治性肝硬化腹水患者的临床疗效观察

目的观察自体骨髓间充质干细胞（BMSC）移植治疗肝硬化难治性腹水的疗效及安全性。方法对2010年9月至2013年9月入住南京总医院消化内科经正规利尿、补充白蛋白达3个月以上且疗效欠佳的32例肝硬化腹水患者,在原有治疗基础上加用自体BMSC移植治疗,分别于治疗前、治疗后1个月及3个月观察腹围、体重、24 h尿量、血清尿素氮、肌酐、尿钠及血清蛋白浓度等指标变化。采用方差分析、配对t检验和Wilcoxon检验进行统计学分析。结果治疗前,患者体重、腹围、24 h尿量及血清尿素氮、肌酐、血清总蛋白、血清白蛋白及尿钠排出水平分别为（66.9±3.8）kg、（94.0±3.6）cm、（966±138.7）ml、（10.5±3.6）mmol/L、（112.4±30.6）μmol/L、（63.8±4.2）g/L、（32.1±2.7）g/L、（43.8±2.3）mmol/L;治疗后1个月,分别为（66.0±3.9）kg、（93.0±3.6）cm、（1032±154.8）ml、（9.9±3.2）mmol/L、（104.8±25.6）μmol/L、（65.3±3.5）g/L、（32.6±2.9）g/L、（44.7±2.7）mmol/L;治疗后3个月,分别为（56.2±3.7）kg、（80.5±4.5）cm、（1530±180.6）ml、（7.9±2.3）mmol/L、（88.7±22.2）μmol/L、（72.8±3.3）g/L、（39.2±1.5）g/L。3个组别8个指标均数比较有统计学意义（F=78.194、117.689、120.527、6.558、6.712、54.827、83.421、493.776,均P=0.000）。治疗后1个月与治疗前水平差异无统计学意义（t分别为0.587、0.636、0.559、0.556、0.678、0.522、0.611、0.592;P=0.331、0.266、0.101、0.416、0.25、0.107、0.447）;而治疗后3个月,患者的体重、腹围较治疗前及治疗后1个月均明显减少,24 h尿量明显增加（与治疗前比较,t=3.722、3.784、3.821,与治疗后1个月比较,t=3.921、3.834、3.944,均P=0.000）,血清尿素氮、肌酐水平较治疗前及治疗后1个月均明显下降;而血清总蛋白、白蛋白及尿钠排出水平均明显升高（与治疗前比较,t=2.182、2.338、2.182、2.412、2.136,P尿素、肌酐=0.001,其余P     

Changes in the walls of autologous venous grafts after transplantation into arteries

In 54 dogs 76 operations on plastics of the common carotid arteries with the femoral vein segments have been performed. The animals have been observed for 3 days--1.5 years. The grafts, preserving their permeability, have been studied using a complex of anatomical, histological and micromorphometric techniques. At early stages after the operation (up to 7 days), dystrophic and necrobiotic changes predominate in the wall of the venous graft. As a result of overstretching of the denervated and devascularized vessel, under the effect of a high arterial pressure, nearly total rejection of the endothelial lining takes place, as well as death of some smooth myocytes in the middle tunic; this determines appearance of early thromboses. During 2-6 months after the operation, against the background of a good revascularization of the graft, restorative and adaptive changes develop in its wall. The intima becomes thick at the expense of formation of the obliquely situating layer of myocytes, as well as the result of parietal thromboses organizing on the deendothelized internal surface. These thickenings are especially well seen in the zones of anastomoses. In 6 months--1.5 years after the transplantation into the artery, as a result of constriction of the vessels feeding the graft and reduction of blood stream along them, atrophic and sclerotic changes increase in the wall. The intimal thickenings often acquire the pattern of fibrous patches, that make the lumen more narrow; this can cause appearance of late occlusions and thromboses of the grafts.     

Long term effect on mortality of stopping smoking after unstable angina and myocardial infarction.

Subjects who stop smoking cigarettes after myocardial infarction have an improved rate of survival compared with those who continue, but to date it was not known whether the benefit persisted for more than six years. A total of 498 men aged under 60 years who had survived a first episode of unstable angina or myocardial infarction by two years were followed up by life table methods for a further 13 years. Mortality in those who continued to smoke was significantly higher (82.1%) than in those who stopped smoking (36.9%). These differences increased with time. Mortality in those who were non-smokers initially and who continued not to smoke was intermediate (62.1%). The adverse effect of continued smoking was most pronounced in those with unstable angina. Continuing to smoke increased the rate of sudden death to a greater degree in those with less severe initial attacks, while the effect of smoking on fatal reinfarctions was most apparent in those with a more complicated presentation. These findings suggest that stopping cigarette smoking is the most effective single action in the management of patients with coronary heart disease.     

Simultaneous achievement of accurate CT number and image quality improvement for myocardial perfusion CT at 320-MDCT volume scanning

PurposeTo investigate differences in image-to-image variations between full- and half-scan reconstruction on myocardial CT perfusion (CTP) study.MethodsUsing a cardiac phantom we performed ECG-gated myocardial CTP on a second-generation 320-multidetector CT volume scanner. The heart rate was set at 60 bpm; once per second for a total of 24 s were performed. CT images were acquired at 80- and 120 kVp and subjected to full- and half-scan reconstruction. On images acquired at the same slice level we then measured image-to-image variations, coefficients of variance (CV), and image noise.ResultsThe image-to-image variations with full- and half-scan reconstruction were 1.3 HU vs. 27.2 HU at 80 kVp (p < 0.001) and 0.70 HU vs. 9.3 HU at 120 kVp (p < 0.001) even though the mean HU value was almost the same for both reconstruction methods. The CV of 80- and 120-kVp images of the left ventricular cavity decreased by 0.16% and 0.17%, respectively, with full-scan reconstruction; with half-scan reconstruction it decreased by 3.34% and 2.30%, respectively. Compared with half-scan reconstruction, the image noise was reduced by 27.2% at 80 kVp and by 28.0% at 120 kVp with full-scan reconstruction.ConclusionMyocardial CTP with full-scan reconstruction substantially decreased image-to-image variations and provided accurate CT attenuation.     

Perilesional intrathecal administration of autologous bone marrow stromal cells achieves functional improvement in pigs with chronic paraplegia

Background aimsAt present, on the basis of the great number of preclinical studies and preliminary clinical trials in humans, bone marrow stromal cell (BMSC) transplantation offers promise in the treatment of paraplegia. Nevertheless, there is not enough experience in humans about the best candidates for this type of cell therapy or details about the best parameters or best route of administration.MethodsTwo adult paraplegic pigs with chronic paraplegia were treated only with perilesional intrathecal administration of 40 × 10⁶ autologous BMSC suspended in autologous plasma and followed for 1 year after cell transplantation.ResultsOur study showed clinical improvement, starting at 2 mo after BMSC administration and reaching stabilization at 10 mo. This was associated with recovery of previously abolished somatosensory-evoked potentials. At the end of the study, histological images suggested spinal cord regeneration.ConclusionsOur present findings suggest the possible utility of perilesional intrathecal administration of autologous BMSC in patients with chronic paraplegia.