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.
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).
ObjectiveTo determine the expression level of Sonic hedgehog (Shh) in the passage of hair follicle stem cells (HFSCs), analyze the effect of Shh overexpression on the proliferation activity of HFSCs, and explore the survival of HFSCs after Shh overexpression and its effect on hair follicle regeneration. MethodsHair follicles from the normal area (H1 group) and alopecia area (H2 group) of the scalp donated by 20 female alopecia patients aged 40-50 years old were taken, and the middle part of the hair follicle was cut under the microscope to culture, and the primary HFSCs were obtained and passaged; the positive markers (CD29, CD71) and negative marker (CD34) on the surface of the fourth generation HFSCs were identified by flow cytometry. The two groups of HFSCs were transfected with Shh-overexpressed lentivirus. Flow cytometry and cell counting kit 8 assay were used to detect the cell cycle changes and cell proliferation of HFSCs before and after transfection, respectively. Then the HFSCs transfected with Shh lentivirus were transplanted subcutaneously into the back of nude mice as the experimental group, and the same amount of saline was injected as the control group. At 5 weeks after cell transplantation, the expression of Shh protein in the back skin tissue of nude mice was detected by Western blot. HE staining and immunofluorescence staining were used to compare the number of hair follicles and the survival of HFSCs between groups. ResultsThe isolated and cultured cells were fusiform and firmly attached to the wall; flow cytometry showed that CD29 and CD71 were highly expressed on the surface of the cells, while CD34 was lowly expressed, suggesting that the cultured cells were HFSCs. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression levels of Shh protein and gene in the 4th, 7th, and 10th passages of cells in H1 and H2 groups decreased gradually with the prolongation of culture time in vitro. After overexpression of Shh, the proliferation activity of HFSCs in the two groups was significantly higher than that in the blank group (not transfected with lentivirus) and the negative control group (transfected with negative control lentivirus), and the proliferation activity of HFSCs in H1 group was significantly higher than that in H2 group before and after transfection, showing significant differences (P<0.05). At 5 weeks after cell transplantation, Shh protein was stably expressed in the dorsal skin of each experimental group; the number of hair follicles and the expression levels of HFSCs markers (CD71, cytokeratin 15) in each experimental group were significantly higher than those in the control group, and the number of hair follicles and the expression levels of HFSCs markers in H1 group were significantly higher than those in H2 group, and the differences were significant (P<0.05). ConclusionLentivirus-mediated Shh can be successfully transfected into HFSCs, the proliferation activity of HFSCs significantly increase after overexpression of Shh, which can secrete and express Shh continuously and stably, and promote hair follicle regeneration by combining the advantages of stem cells and Shh.
Objective To establish a model of transplanting neonatal cardiomycytes into the wall of rat inferior vena cava. Methods Neonatal cardiomyocytes (n=6, 5×106cells each, A group) or medium (n=6, B group) only were transplanted into the wall of inferior vena cava in female Fisher rats. At 21 days after transplantation, the contraction of transplanted cardiomyocytes was assessed and the inferior vena cava was processed for histology. Results Distinct rhythmic beating of the vena cava at the site of cell transplantation before and after the aorties were clamped (at a rate 141± 47 rpm and 88± 44 rpm which was dramaticly lower than aortic beating, with a statistical difference at P value of 0.03). Cardiomyocyte was seen in 6 rats who had neonatal cardiomyocyte transplantation, but not in 6 rats receiving media. Hematoxylin and eosin staining showed viable cardiomyocytes in the wall of the vena cava in 6 rats treated with neonatal cardiomyocytes, but not in 6 rats receiving media. Conclusion This study shows that neonatal cardiomyocytes can survive, mature and spontaneously and rhythmically contract after they are transplanted in the wall of inferior vena cava.
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.
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 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.
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.
Ocular fundus diseases is a kind of ophthalmic diseases that occur in the vitreous, retina, choroid and optic nerve, including a series of pathophysiological changes such as inflammation, exudation and proliferation. Because of high morbidity and high blindness rate, ocular fundus diseases has been paid more and more attention from medical community. With the continuous deepening of research on its etiology, anatomy and pathological mechanism in recent years, clinicians have obtained more abundant treatment methods than in the past, and the medical treatment of ocular fundus diseases have made many phased progress. However, due to its wide spectrum of diseases and complex pathological mechanism, clinicians still need to further explore more effective treatment methods, and improve the effect of diagnosis and treatment to ocular fundus diseases.