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.
Cytomegalovirus (CMV) retinitis (CMVR) is a common opportunistic infection of the eye after allogeneic hematopoietic stem cell transplantation in patients with hematological diseases. It often occurs within 3 months after the operation, with CMV activation and high blood CMV peaks. It often occurs on patients with long-term CMV viremia, human leukocyte antigen incompatible transplantation, unrelated donor transplantation, haploid transplantation, childhood hematopoietic stem cell transplantation, delayed lymphocyte engraftment, acute and chronic graft-versus-host disease after surgery. The visual prognosis of patients is related to the area of CMVR lesions on the retina, the number of quadrants involved, whether the macula is involved, and the CMV load of the vitreous body is involved, and it is not related to whether the Epstein-Barr virus infection is combined with blood and vitreous humor. The incidence of CMVR is increasing year by year. It is helpful that paying attention to systemic risk factors and epidemiology can provide more effective guidance for ophthalmologists during diagnosis and treatment, help patients improve the prognosis of vision, and reduce or even avoid the occurrence of blindness caused by CMVR.
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 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 clinical features of cytomegalovirus (CMV) retinitis (CMVR)-related uveitis after hematopoietic stem cell transplantation (HSCT).MethodsA retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12±12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.ResultsAll eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.ConclusionCMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (＞3 months).
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.
ObjectiveTo observe the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on blood glucose levels and diabetic retinopathy in diabetes mellitus (DM) rats. MethodA total of 45 healthy male Sprague-Dawley rats were randomly divided into normal control group (group A, 10 rats) and DM group (33 rats). Diabetic model was established in DM group by tail vein injection of streptozotocin.The DM group was further randomly divided into 3 groups (11 rats in each group), including group B (no transplantation), group C (hUCMSC was injected through tail vein) and group D (hUCMSC was injected into the vitreous). Blood glucose, retina wholemont staining and expression of brain derived neurotrophic factor (BDNF) in the retina were measured at 2, 4, 6, 8 weeks after hUCMSC injection. The blood glucose was significantly different between A-D groups before injection (t=-64.400, -60.601, -44.065, -43.872; P=0.000) BDNF expression was studied by real time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry staining. ResultsThe blood glucose was significantly different between A-D groups after hUCMSC injection (F=400.017, 404.410, 422.043, 344.109; P=0.000), and between group C and group B/D (t=4.447, 4.990; P < 0.01). Immuno-staining shown that BDNF was positive in ganglion cell layer (RGC) of group A, weak in group B while BDNF expression increased in group C/D. BDNF mRNA expression was significantly different between group B, C and D at 4, 6 and 8 weeks after hUCMSC injection (F=29.372, 188.492, 421.537; P=0.000), and between group B and C/D (t=66.781, 72.401, 63.880, 88.423, 75.120, 83.002; P < 0.01) by RT-PCR analysis. The BDNF mRNA expression was significantly different between C and D groups only at 8 weeks after hUCMSC injection (t=127.321, P=0.005). ConclusionsTail vein injection of hUCMSCs can significantly reduce the blood glucose levels of rats. Intravenous and intravitreal injection of hUCMSCs can increase the expression of BDNF.
ObjectiveTo observe the protective effect of human umbilical cord blood stem cells (hUCBSC) transplantation on retinal ganglion cells (RGC) after optic nerve injury. Method48 adult Sprague-Dawley rats were randomly divided into group A and B, therefore 24 rats in each group. Calibrated optic nerve crush injury model was induced in the left eyes, the right eyes served as a control. Medicine was injected at seventh day after optic nerve injury. PBS was injected into the eyes of Group A rats by peribulbar injection. The hUCBSCs were injected into the eyes of Group B rats by peribulbar injection. Seven days before sacrifice, 5% fluorogold was injected into superior colliculi bilaterally. At 7, 14, 21, 28 days after labeled, retinal flat mounts were observed under fluorescence microscope and optical microscope to investigate the morphological and RGC changes in density during retinal degeneration. ResultsThe RGC number showed a tendency to decline gradually along with increases of the time in two groups, but the trend of decrease of Group B was evidently slower than that of Group A. The RGC number of the injury eye were less than the control eye in Group A and B (t=3.24, 3.15; P < 0.05). At 7, 14, 21, 28 days after labeled, the RGC number (t=4.78, 4.70, 3.98, 3.27; P < 0.05) and labeled RGC rate (t=4.39, 4.21, 4.36, 5.07; P < 0.05) in group B were more than those in group A. After optic nerve injury, there was karyopycnosis on ganglion cell layer of retina, thinning on each layer of retina, derangement of cell and decrease in RGC. There was different degree of the above change in different time after optic nerve injury. There were the swelling, the hemorrhage, derangement of spongiocyte and the denaturation like vacuole in the spot of optic nerve injury. Moreover, they were aggravating with increases of the time after optic nerve injury. There was no pathological changes in normal eyes. ConclusionThe hUCBSC can increase the survival rate of the RGC and can rescue and(or) restore the injujed RGC after transplanted into body of optic nerve crush rat model by peribulbar injection.
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.
ObjectiveTo systematically review the efficacy and safety of non-myeloablative stem cell transplantation (NST) for the treatment of multiple myeloma (MM) after first autologous stem cell transplantation. MethodsSuch databases as The Cochrane Library (Issue 5, 2013), PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were electronically searched to collect studies investigated the efficacy and safety of NST and non-NST for the treatment of MM after first autologous stem cell transplantation from the date of their establishment to June 13th 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.1 software. ResultsSeven studies involving 1 961 participants were included, of which 626 cases were in the NST group and 1 335 cases were in the non-NST group. The results of meta-analysis showed that no significant difference was found between both groups in the overall survival rate (HR=1.06, 95%CI 0.78 to 1.44, P=0.69) and progress-free survival rate (HR=0.92, 95%CI 0.76 to 1.11, P=0.39). However, there were significant differences in the complete remission rate (RR=1.29, 95%CI 1.13 to 1.48, P=0.000 2) and treatment-related mortality rate (RR=3.40, 95%CI 2.27 to 5.07, P < 0.000 01). ConclusionThe efficacy of NST is not superior to non-NST for patients with MM which has received first autologous stem cell transplantation. It is not sufficient to recommend NST as the first-line treatment of MM based on the currently available evidence.
