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Bing Chen,
Min Zhou,
Jian Ouyang,
Rongfu Zhou,
Jingyan Xu,
Qiguo Zhang,
Yonggong Yang,
Yong Xu,
Xiaoyan Shao, Li Meng,
Jing Wang,
Yun Xu,
Xiushi Ni,
Xueguang Zhang
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ABSTRACT: Autologous haematopoietic stem cell transplantation (AHSCT) is a promising treatment for multiple sclerosis (MS) patients who have not adequately responded to conventional therapies. We retrospectively evaluated the safety and long-term clinical outcome of AHSCT in MS patients in China. Twenty-five patients with various types of MS were treated with AHSCT. Peripheral blood stem cells were derived by leukapheresis after mobilized with granulocyte colony-stimulating factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion, with the conditioning regimen BEAM adopted and early and late toxicities recorded. Long-term responses were evaluated by the expanded disability status scale (EDSS), progression-free survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8 patients experienced neurological improvement, stabilization and progression, respectively. The median EDSS scores observed over 1-year follow-up after transplantation (5.5-7.0) were consistently lower than the baseline (8.0). The progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post-transplant. 58% cases (7/12) had active lesions at baseline and all turned to inactive status in the years of follow-up. 25% cases (3/12) experienced progression after transplantation but had no active lesions in MRI over the whole follow-up period. 17% cases (2/12) without active lesions at baseline progressed active lesions in MRI. The major early toxicity resulted in fever and late toxicity caused transplantation-related mortality due to severe pneumonia and varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for severe MS and its long-term efficacy is favorable.
Neurological Sciences 12/2011; 33(4):881-6. · 1.32 Impact Factor
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ABSTRACT: Early-phase clinical trials suggest that autologous bone-marrow-derived cells (BMCs) may have a positive effect on patients with severe peripheral arterial disease (PAD). However, the therapeutic effects of BMCs treatment in various aspects remain controversial.
We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with severe PAD. Pubmed, EMBASE, EBSCO and the Cochrane Central Register of Controlled Trials ( to approximately April 2011) were searched.
Seven RCTs with 276 patients were included. Pooled comparisons of studies found that BMCs therapy significantly improved ankle-brachial index (ABI) by 0.10 (95% CI, 0.07 to 0.14; p < 0.00001), transcutaneous oxygen tension (TcO(2)) by 13.39 mmHg (95% CI, 6.69 to 20.1 mmHg; p < 0.0001) and pain-free walking distance by 119.91 m (95% CI, 90.71 to 149.11 m; p < 0.00001). BMCs therapy significantly decreased scale of rest pain by 1.13 (95% CI, -1.71 to -0.54, p = 0.0002) and helped heal ulcers (OR, 7.17; 95% CI, 2.66 to 19.32; p < 0.0001).
Our analysis based on seven RCTs suggests that autologous BMCs therapy, has a beneficial effect on physiologic and anatomic parameters in patients with severe PAD.
Expert opinion on biological therapy 12/2011; 11(12):1581-9. · 3.22 Impact Factor
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ABSTRACT: Previous evaluation of intracoronary autologous bone marrow-derived stem cell (BMSCs) therapy following ischemic heart disease (IHD) suggested improvement of cardiac functional parameters. We performed a meta-analysis to provide systematic assessment of the safety and efficacy of direct (intramyocardial or endomyocardial) BMSCs transplantation in patients with IHD.
Randomized controlled Trials (RCTs) were identified in the MEDLINE (approximately Oct. 2010), the Cochrane Central Register of Controlled Trials (Central) (approximately Oct. 2010), EMBASE (approximately Oct. 2010), and EBSCO (approximately Oct. 2010), reviews, and reference lists of relevant articles. Weighted mean difference (WMD) was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) by using a fixed effects model.
Eight RCTs with 307 participants were eligible. Compared with controls, direct BMSCs transplantation improved LVEF (8.4%, 95% CI, 6.49 to 10.31%; p < 0.01), reduced LVESV and LVEDV (-14.85 ml, 95% CI, -27.29 to -2.41 ml, p = 0.02 and -12.79 ml, 95% CI, -24.94 to -0.65 ml, p = 0.04, respectively).
This meta-analysis suggests that direct BMSCs transplantation is associated with moderate but significant improvements over regular therapy in cardiac functional parameters in patients with IHD, and supports conducting further RCTs of a higher quality.
Expert opinion on biological therapy 03/2011; 11(5):559-67. · 3.22 Impact Factor
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ABSTRACT: Hematopoietic stem cell transplantation (HSCT) has been proposed as a novel therapy for multiple sclerosis (MS). CD4 + CD25 + regulatory T cells (Tregs) expressing Foxp3 play an important role in the maintenance of immune tolerance to self. Our study was conducted to confirm the efficiency of nonmyeloablative conditioning and syngeneic bone marrow transplantation (BMT) on experimental autoimmune encephalomyelitis (EAE) mice and to determine whether Tregs plays a role in the underlying mechanism.
EAE were induced in C57BL/6 mice and were randomly divided into 4 groups: the Conditioning group received the conditioning regimen, the Normal-EAE BMT group received conditioning and bone marrow (BM) grafts from normal mice, the EAE-EAE BMT group received conditioning and BM grafts from EAE mice and the EAE control group received no further therapy. The cumulative clinical score was used to assess the efficacy of the different treatments, and the proportion of Tregs in the spleen was measured by flow cytometry on day 40, 80 and 120 after BMT. Foxp3 mRNA expression was assessed by real-time PCR, and the expression of Foxp3 protein was tested by western blot on day 120 after BMT.
Conditioning and conditioning with BMT led to a significant clinical improvement on day 80 after BMT compared with EAE without further treatment. On day 120 after BMT, the clinical score of the Conditioning group showed no significant difference from that of the EAE control group, whereas BMT led to a further amelioration of the disease score. On day 80 and day 120 after BMT, the proportions of Tregs of the two BMT groups were significantly higher than that in EAE control group, whereas no statistically significant difference was found between the Conditioning group and the EAE control group. On day 120 after BMT, the Foxp3 mRNA level and Foxp3 protein expression was higher in the two BMT groups than in EAE control group or Conditioning group.
Nonmyeloablative conditioning could temporarily reverse already established EAE, but it was not sufficient for the induction of long-term EAE remission. Transplantation by BM cells from healthy or diseased donors was necessary and responsible for complete and long-time remission of EAE, and these beneficial effects may be the result of the induction of Tregs and the Treg-related factor Foxp3.
Restorative neurology and neuroscience 01/2011; 29(3):177-85. · 2.51 Impact Factor
