ObjectiveTo summarize the advances of precl inical research in xenogeneic (porcine) cell transplantation in recent years. MethodsThe literature about the precl inical research in xenogeneic (porcine) cell transplantation was analyzed and summarized. ResultsWith the application of new immunosuppressive agents and the generation of transgenic pigs, great progress has been achieved in xenogeneic transplantation of pig-derived nerve cells, islet cells, liver cells, and various types of stem cells. The survival time of xenogeneic cell (porcine) significantly prolonged, but there is still a long way to go before cl inical application. ConclusionThe source of xenogeneic (porcine) cells is abundant and the experiments are reproducible. However, how to effectively prevent rejection and prolong the survival time in the host, and avoid the spread of virus between species are still need to be solved in the future research.
ObjectiveTo observe the influence of human umbilical cord mesenchymal stem cells (hUCMSC) transplantation into vitreous cavity of diabetic rats on the retinal morphology, and the expression of glial fibrillary acidic protein (GFAP) and rhodopsin (RHO). Methods78 male Sprague-Dawley rats were used. 70 rats were injected with streptozotocin by tail vein injection at a dose of 40 mg/kg to establish the diabetes mellitus model, and another 8 rats were injected with 0.1 mol/L pH 4.0 citric acid buffer at the same dose as the normal control group. After 6 weeks of modeling, 10 rats were taken as the control group of diabetic model. hUCMSC suspension was injected into the right eye vitreous cavity of the remaining 60 rats, and the same volume of Dulbecco's modified Eagle/F12 medium was injected into the left vitreous cavity as control eyes. 1, 2 and 4 weeks after transplantation, follow-up experiments were performed. The experimental eyes were labeled as U1, U2, and U4 groups, while the control eyes were recorded as D1, D2, D4, and each group consisted of 20 eyes. After paraffin section and hematoxylin-eosin staining, the structure of the retina was observed by optical microscopy and the thickness of the outer nuclear layer and the inner nuclear layer (INL) were measured. The distribution and migration of hUCMSC in rat retina were observed by frozen section-tissue immunofluorescence assay. The mRNA and protein expression of GFAP and RHO in the retina were detected by real-time quantitative polymerase chain reaction (PCR) and Western blot assays. ResultsThe results of optical microscope observation showed the normal structure of retina in normal control group. The retinal nerve fiber layer (NFL) was thinned and the number of retinal ganglion cells (RGC) in the control group of diabetic rats was decreased. The decreased number and disorder arrangement of RGC were observed as well in U1, D1 rats. The RGC number of U2, U4, D2, D4 rats was gradually decreased. Compared with D4 group, the thickness of INL in U4 group was significantly increased (P < 0.05). Tissue immunofluorescence assay showed that hUCMSC were distributed along the inner limiting membrane in the retina of the U1 group, while the number of hUCMSC in the U2 group was gradually decreased, mainly in the NFL and ganglion cell layers. Real-time PCR and Western blot data indicated that the relative expression of GFAP mRNA and protein in the diabetic retina was significantly increased, and the relative expression of RHO mRNA and protein decreased gradually in the diabetic model group and the D1, D2, D4 groups. Compared with D2 and D4 groups, the mRNA and protein expression of GFAP in U2 and U4 groups were decreased, and the relative expression of RHO mRNA and protein were all increased (P < 0.01). ConclusionhUCMSC could migrate and integrate into the retina, after the transplantation into the vitreous cavity of diabetic rats, which reduced the expression of GFAP, but enhanced the expression of RHO.
Objective To review the value of imaging assessment of stem cell transplantation in treatment for liver cirrhosis.Methods The related literatures in recent years were collected,and the applications of different radiological techniques and strategies of stem cell transplantation in treatment for liver cirrhosis were summarized.Results Stem cell transplantation in treatment for liver cirrhosis was feasible and effective. Radiological assessment could supply the prompt and accurate information for clinic to choose the proper therapeutic method.The curative effect could also be accurately assessed by radiological techniques.Conclusion Radiological examination is important for the assessment of stem cell transplantation in treatment for liver cirrhosis.
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.
ObjectiveTo observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment. MethodsA retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration. ResultsAt the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [R2=0.385, P＜0.000 1, B=－0.237 log10 copies/(ml · time)], and the duration of treatment [R2=0.394, P <0.000 1, B=－0.301 log10 copies/(ml · week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity (t=－1.223), intraocular pressure (t=1.538), aqueous humor CMV-DNA load (t=－0.109), retinitis lesion area (Z=－0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved (Z=－0.024) and whether the macula was involved (Z=－1.826), combined with anterior segment inflammation (Z =－0.499), combined with high intraocular pressure (Z=－1.342), terminal visual acuity (t =－0.845), intraocular pressure (t=－0.068), total IVG times (Z=0.907), age (Z=－0.832), gender composition (Z=－1.074), etc. The difference was not statistically significant (P＞0.05). ConclusionThe CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.
Stargardt disease (STGD) is one of the most prevalent inherited macular dystrophy, and most often occurs in child or adolescence. Irreversible vision loss is observed in almost all cases. Type 1 (STGD1) is one of the most common type. It is an autosomal recessive condition, caused by mutations in the Abca4 gene. In recent years, encouraging progress has been made in the treatment of STGD1. C20-D3-retinyl acetate (ALK-001), fenretinide and ICR-14967 (A1120) as visual cycle modulators, StarGen as gene supplementation therapies, and the stem cell transplantation of human embryonic stem cell-derived retinal pigment epithelium cells are the most promising therapies. With the development of studies and clinical trials, the clinical application of various treatments of STGD1 are expected in the near feature, which are expected to save the vision of most patients.
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 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.
Objective To observe the effects of the bone marrow mesenchymal stem cells (BMSCs) on the expression of neurotrophic factor protein gene in the retinal detachment (RD) rabbits. Methods 60 healthy rabbits were randomly divided into control group (group A), retinal detachment with PBS group (group B), retinal detachment with BMSCs group (group C), 20 rabbits in each group. RD model were established for rabbits in group B and C. 10 μl PBS was injected into the subretinal space of rabbits in group B, while 10 μl CM-Dil labeled BMSC PBS was injected into subretinal space of rabbits in group C. The rabbits in the group A received no treatment. At 1, 2 and 4 weeks after modeling, the mRNA expression of basic fibroblast growth factor (bFGF), brain derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) were measured by real-time quantitative PCR. Results At 1, 2 and 4 weeks after modeling, the mRNA expression of bFGF, BDNF, CNTF on retinal tissue were increased significantly in group C as compared with group A and B (P < 0.01). At 1 week after modeling, the mRNA expression of bFGF and CNTF on retinal tissue were increased significantly in group B as compared with group A, the mRNA expression of BDNF on retinal tissue in group B was similar with group C. At 2 and 4 weeks after modeling, the mRNA expression of bFGF, BDNF, CNTF were decreased in group B as compared with group A. Conclusion Subretinal transplantation of BMSC can increase the mRNA expression of bFGF, BDNF and CNTF on retinal tissue in RD rabbits.
Objective To evaluate the effect of smooth muscle cell transplantation on myocardial interstitial reconstruction shortly after myocardial infarction. Methods A total of 48 female Wister rats were randomly divided into two groups with the random number table, the control group (n=24) and the smooth muscle cell transplantation group (n=24). The left coronary artery was ligated to set up the myocardial infarction animal model. An amount of 05 ml phosphate buffered saline(PBS) containing 1×106 smooth muscle cells or 0.5 ml PBS without cells was injected into the injured myocardium immediately. By immunoblot and reverse transcriptionolymerase china reaction (RT-PCR), we observed the amount of protein and mRNA of matrix metalloproteinase2(MMP-2), matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloprotease-3 (TIMP-3) in the myocardium of the rats. Results The transplanted smooth muscle cells survived well. Compared with the control group, myocardial TIMP3 mRNA (1.06±0.22 vs. 0.81±0.19, t=－2.358, P=0.033) and protein content (3.33±0.53 vs. 1.63±0.47, t=－6.802, Plt;0.001) were significantly increased in the transplantation group. Myocardial MMP-2, MMP-9 mRNA (0.49±0.12 vs. 1.16±0.18, t=8.453, Plt;0.001; 0.45±0.12 vs. 0.80±0.11, t=5.884, Plt;0.001) and protein content (3.98±1.08 vs. 6.05±0.91, t=4.139, P=0.001; 0.39±0.14 vs. 0.57±0.17, t=2.409, P=0.031) [CM(1585mm]were significantly reduced in the transplantation group compared with the control group. Conclusion transplanted smooth muscle cells can survive well in the infarction myocardium and can increase the amount of myocardial TIMP-3 mRNA and protein content and reduce myocardial MMP-2, MMP-9 mRNA and protein content, which is an effective way to prevent harmful cardiac remodeling.