Objective To assess systematically the safety and ef fects of stem cell transplantation in stroke patients.Methods CENTRAL (April 2007), MEDLINE (1966 to April 2007), EMBASE (1980 to April 2007), and other databases were searched for RCT of the use of stem cell transplantation for patients with stroke. We critically appraised the quality of included studies according to Juny 2001. We assessed the effects of stem cell therapy on mortal ity, functional outcomes, cognitive functions, image changes, quality of life, and adverse effects by doing meta-analysis with The Cochrane Collaboration’ s Review Manager. Dichotomous outcomes were reported as relative risk and continuous outcome measures as weighted mean differences, with 95% confidence intervals.Results Three RCTs and one historical controlled trial were included involving a total of 69 participants. Only one trial reported the effect on mortality, but because of the small number of death it was not possible to detect any significant differences between stem cell transplantation and routine treatment (RR 0.11, 95%CI 0.01 to 2.31, P = 0.16). Three studies indicated a statistically significant improvement of some functional outcomes in patients treated by stem cell transplantation. Improvements of cognitive function were reported in another trial. One trial showed that the stem cell transplantation significantly improved qual ity of life compared with the control group. Conclusion The current evidence is insufficient to determine whether or not stem cell transplantation is a safe and effective therapy for stroke patients. High-quality, large-scale randomized trials are needed to assess the role of stem cell transplantation for stroke.
Objective To observe the effects of subretinal transplantation of rat mesenchymal stem cells (rMSCs) on Sodium Iodate (SI)induced retinal degeneration. Methods One hundred and twenty BrownNorway (BN) rats were divided into three groups including SI injection group,rMSCs transplantation group and normal control group, each with 40 rats. The retinal degeneration was induced by caudal vein injection of SI. The retinal pigment epithelium（RPE）and neural retinal were evaluated by ocular fundus photograph, fluorescein fundus angiography (FFA)，electroretinogram (ERG) and histological approach, and TUNEL（terminal deoxynucleotidyl transferasemediated dUTP nick end labeling ）. CMDiIprelabeled primary rMSCs were transplanted into the subretinal space of SIinduced rats. The survival, integration, and differentiation of rMSCs were observed between 14 day to 60 day after the transplantation.Results The rat retinal function was gradually reduced after14 days of SI injection, with a timedependent manner. After the RPE cells were damaged，the outer segments of photoreceptors became disrupted and shortened until karyopyknosis. The nuclear morphology and positive TUNEL labeling indicated that the death of photoreceptor cells was apoptosis. After rMSCs transplantation, CMDiI labeled donor cells were observed to be scattered in the subretinal space and expressed RPE cell markers. Average amplitude of b wave and Ops (oscillation potential) in ERG improved 27.80%,59.38% respectively after rMSCs transplantation.Conclusions Transplanted rMSCs can survive in subretinal space and differentiate into RPE.
ObjectiveTo observe the morphological and functional changes of retinal degeneration in mice with CLN7 neuronal ceroid-lipofuscinosis, and the therapeutic effects of glial cell derived neurotrophic factor (GDNF) and/or ciliary neurotrophic factor (CNTF) based on neural stem cells (NSC) on mouse photoreceptor cells. MethodsA total of 100 CLN7 mice aged 14 days were randomly divided into the experimental group and the control group, with 80 and 20 mice respectively. Twenty C57BL/6J mice aged 14 days were assigned as wild-type group (WT group). Mice in control group and WT group did not receive any interventions. At 2, 4, and 6 months of age, immunohistochemical staining was conducted to examine alterations in the distribution and quantity of cones, rod-bipolar cells, and cone-bipolar cells within the retinal of mice while electroretinography (ERG) examination was utilized to record scotopic a and b-waves and photopic b-wave amplitudes. At 14 days of age, the mice in the experimental group were intravitreally injected with 2 μl of CNTF-NSC, GDNF-NSC, and a 1:1 cell mixture of CNTF-NSC and GDNF-NSC (GDNF/CNTF-NSC). Those mice were then subdivided into the CNTF-NSC group, the GDNF-NSC group, and the GDNF/CNTF-NSC group accordingly. The contralateral eyes of the mice were injected with 2 μl of control NSC without neurotrophic factor (NTF) as their own control group. At 2 and 4 months of age, the rows of photoreceptor cells in mice was observed by immunohistochemical staining while ERG was performed to record amplitudes. At 4 months of age, the differentiation of grafted NSC and the expression of NTF were observed. Statistical comparisons between the groups were performed using a two-way ANOVA. ResultsCompared with WT group, the density of cones in the peripheral region of the control group at 2, 4 and 6 months of age (F=285.10), rod-bipolar cell density in central and peripheral retina (F=823.20, 346.20), cone-bipolar cell density (F=356.30, 210.60) and the scotopic amplitude of a and b waves (F=1 911.00, 387.10) in central and peripheral retina were significantly decreased, with statistical significance (P＜0.05). At the age of 4 and 6 months, the density of retinal cone cells (F=127.30) and b-wave photopic amplitude (F=51.13) in the control group were significantly decreased, and the difference was statistically significant (P＜0.05). Immunofluorescence microscopy showed that the NSC transplanted in the experimental group preferentially differentiated into astrocytes, and stably expressed CNTF and GDNF at high levels. Comparison of retinal photoreceptor nucleus lines in different treatment subgroups of the experimental group at different ages: CNTF-NSC group, at 2 months of age: the whole, central and peripheral regions were significantly different (F=31.73, 75.06, 75.06; P＜0.05); 4 months of age: The difference between the whole area and the peripheral region was statistically significant (F=12.27, 12.27; P＜0.05). GDNF/CNTF-NSC group, 2 and 4 months of age: the whole (F=27.26, 27.26) and the peripheral area (F=16.01, 13.55) were significantly different (P＜0.05). In GDNF-NSC group, there was no statistical significance at all in the whole, central and peripheral areas at different months of age (F=0.00, 0.01, 0.02; P＞0.05). ConclusionsCLN7 neuronal ceroid-lipofuscinosis mice exhibit progressively increasing degenerative alterations in photoreceptor cells and bipolar cells with age growing, aligning with both morphological and functional observations. Intravitreal administration of stem cell-based CNTF as well as GDNF/CNTF show therapeutic potential in rescuing photoreceptor cells. Nevertheless, the combined application of GDNF/CNTF-NSC do not demonstrate the anticipated synergistic protective effect. GDNF has no therapeutic effect on the retinal morphology and function in CLN7 neuronal ceroid-lipofuscinosis mice.
ObjectiveTo analyze the efficacy and safety of various treatment strategies for patients with refractory/recurrent diffuse large B-cell lymphoma (r/r-DLBCL) by network meta-analysis. MethodsThe PubMed, EMbase and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) and clinical controlled trials related to the objectives of the study from inception to November 16th, 2022. After two investigators independently screened the literature, extracted data and evaluated the risk of bias of the included studies, a network meta-analysis was performed using R 4.2.2 software. ResultsA total of 8 RCTs and 11 non-randomized controlled trials were included, involving 2 559 cases. The treatment regimen included chemotherapy, immunochemotherapy, chemotherapy combined with ADC, immunochemotherapy combined with ADC, ASCT based regimen, CAR-T based regimen, ASCT combined with CAR-T, immunomodulators, small molecule inhibitors, and rituximab combined with small molecule inhibitors. The ranking probability results showed that the top three complete remission (CR) rates among all schemes were ASCT combined with CAR-T, chemotherapy combined with ADC, and immune modulators; The top three overall response rates (ORR) were chemotherapy combined with ADC, ASCT combined with CAR-T, and ASCT. The CAR-T regimen had a higher rate of severe neutropenia; The severe thrombocytopenia rate of ASCT regimen was relatively high; There was no significant difference in the incidence of SAEs among the other options. ConclusionASCT combined with CAR-T and chemotherapy combined with ADC have the best therapeutic effects on r/r-DLBCL. However, the specific protocol to be adopted requires clinical doctors to combine actual conditions, comprehensively consider the efficacy and side effects, and develop personalized treatment strategies for r/r-DLBCL patients.
ObjectivesTo systematically review the efficacy and safety of palifermin on oral mucositis (OM) and acute graft versus host disease (aGVHD) for hematological malignancy patients undergoing hematopoietic stem cell transplantation (HSCT).MethodsPubMed, The Cochrane Library, Web of Science, EMbase, Clinicaltrials.gov, CNKI and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) of the efficacy of palifermin on OM and aGVHD for hematological malignancy patients undergoing HSCT from inception to September 30th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 7 RCTs involving 904 patients were included. The results of meta-analysis showed that: palifermin could reduce the duration of OM grade 2 to 4 (MD=−4.21, 95%CI −7.83 to −0.58, P=0.02), OM grade 3 to 4 (MD=−2.54, 95%CI −4.61 to −0.46, P=0.02) significantly for hematological malignancy patients undergoing HSCT. However, no significant difference was found in the prevalence of aGVHD grade 2 to 4 (RR=1.29, 95%CI 0.95 to 1.75, P=0.11), aGVHD grade 3 to 4 (RR=0.99, 95%CI 0.55 to 1.77, P=0.97), OM grade 2 to 4 (RR=0.86, 95%CI 0.72 to 1.03, P=0.11) and OM grade 3 to 4 (RR=0.82, 95%CI 0.65 to 1.03, P=0.08) between palifermin group and placebo group. The prevalence of paresthesia (RR=4.24, 95%CI 1.24 to 14.56, P=0.02) and erythema (RR=1.49, 95%CI 1.06 to 2.09, P=0.02) were significantly higher in palifermin group.ConclusionsThe durations of OM grade 2 to 4, 3 to 4 are significantly reduce in patients receiving palifermin compared with those receiving a placebo, however, no statistically significant difference are found in the incidence of aGVHD grade 2 to 4, 3 to 4, OM grade 2 to 4, 3 to 4. Parethesia and erythema are more prevalent among patients using palifermin. Therefore, advantages and disadvantages of palifermin should be considered when used in clinical.
Objective To summarize the research progress of stem cell transplantation in treating spinal cord injury (SCI) at different stages based on the pathophysiological mechanism of SCI. Methods The relevant research literature at home and abroad was extensively reviewed to explore the impact of transplantation timing on the effectiveness of stem cell transplantation in treating SCI. Results Researchers performed different types of stem cell transplantation for subjects at different stages of SCI through different transplantation approaches. Clinical trials have proved the safety and feasibility of stem cell transplantation at acute, subacute, and chronic stages, which can alleviate inflammation at the injured site and restore the function of the damaged nerve cells. But the reliable clinical trials comparing the effectiveness of stem cell transplantation at different stages of SCI are still lacking. Conclusion Stem cell transplantation has a good prospect in treating SCI. In the future, the multi-center, large sample randomized controlled clinical trials are needed, with a focus on the long-term effectiveness of stem cell transplantation.
ObjectiveTo systematically review clinical efficacy and safety of bone marrow stem cells transplantation in treating primary dilated cardiomyopathy (DCM). MethodsSuch databases as PubMed, CENTRAL, EMbase, Web of Knowledge, VIP, CNKI, CBM and WanFang Data were searched from inception to March 2014 for the randomized controlled trials (RCTs) about bone marrow stem cells transplantation for DCM. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data, and assessed methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2.0 software. ResultsA total of ten RCTs involving 374 patients were included. The results of meta-analysis showed that, a) for safety, after 3 months there was no significant difference in the incidence of malignant arrhythmia events between bone marrow stem cell transplantation group and routine treatment group (RR=0.81, 95%CI 0.38 to 1.72, P=0.58); and b) for efficacy, compared with the control group, left ventricular ejection fraction (LVEF) increased in the bone marrow stem cell transplantation group after 3 months (WMD=3.86, 95% CI 2.53 to 5.20, P<0.000 01) and after 6 months (WMD=5.54, 95%CI 3.02 to 8.06, P<0.000 1). The bone marrow stem cell transplantation group were better in increased 6-minute walking distance after 3 months (WMD=22.12, 95%CI 7.78 to 36.46, P=0.003), increased 6-minute walking distance after 6 months (WMD=102.79, 95%CI 50.16 to 155.41, P=0.000 1), decreased perfusion defect of myocardium percentage after 3 months (WMD=-4.00, 95%CI -5.87 to -2.13, P<0.000 1). However, there was no significant difference in left ventricular end-diastolic diameter (LVEDD) between two groups after 3 months (WMD=-0.37, 95%CI -1.67 to 0.93, P=0.57) and after 6 months (WMD=-0.70, 95%CI -2.76 to 1.36, P=0.51). ConclusionBone marrow stem cells transplantation for dilated cardiomyopathy is effective in improve patients' heart function with good safety, with significant difference. Due to limited quantity and quality of the included studies, more high quality and large-scale RCTs are needed to verify the above conclusion.