Objective To review and summarize the latest development of the therapy for the Duchenne muscular dystrophy (DMD). Methods Therecentlypublished articles related to the therapies for DMD were extensively reviewed and briefly summarized. Results The therapeutic approaches for DMD included the gene therapy, the cell therapy, and the pharmacological therapy. The gene therapy and the cell therapy were focused on the treatment for the cause of DMD by the delivery of the missing gene, the modification of the mutated gene, and the transfer of the normal cells including the stem cells, while the pharmacological therapy dealt with the downstream events caused by the dystrophin gene defect, slowed down the pathologic progress of DMD, and improved the DMD patient’s life quality and life span, by medication and other factor treatments. Conclusion There is still no cure for DMD because of various difficulties in replacing or repairing thedefected gene and of the multifaceted nature of the severe symptoms. Therefore,it is imperative for us to find out a more effective treatment that can solve these problems.
Objective To summarize the recent progress of cell-based approaches for promoting bone regeneration in distraction osteogenesis (DO). Methods Recent literature concerning enhancement of bone regeneration following DO using cell-based approaches was reviewed and analyzed. Results An overview of 4 different cell-based approaches was mainly provided: single cell injection, cell scaffold-based strategies/injectable tissue engineered bone, microtissue technology or cell aggregate technology, and stem cell gene therapy. Each has its advantages and disadvantages. Other methods are still in the experimental research except that compound injection of bone marrow mesechymal stem cells and platelet-rich plasma has been applied to clinical practice. Conclusion The cell-based approach is a promising strategy in the field of bone regenerative medicine. These approaches have bright future in promoting bone regeneration and reducing the treatment period in DO in the clinical application. However, well-designed preclinical studies are required to establish safe and effective guidelines for cell-based approaches to promoting bone regeneration during DO.
Hereditary ocular fundus disease is an important cause of irreversible damage to patients' visual acuity. It has attracted much attention due to its poor prognosis and lack of effective clinical interventions. With the discovery of a large number of hereditary ocular fundus genes and the development of gene editing technology and stem cell technology, gene and stem cell therapy emerged as the new hope for curing such diseases. Gene therapy is more directed at early hereditary ocular fundus diseases, using wild-type gene fragments to replace mutant genes to maintain existing retinal cell viability. Stem cell therapy is more targeted at advanced hereditary ocular fundus diseases, replacing and filling the disabled retinal cell with healthy stem cells. Although gene and stem cell therapy still face many problems such as gene off-target, differentiation efficiency, cell migration and long-term efficacy, the results obtained in preclinical and clinical trials should not be underestimated. With the emergence of various new technologies and new materials, it is bound to further assist gene and stem cell therapy, bringing unlimited opportunities and possibilities for the clinical cure of hereditary ocular fundus diseases.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
Abstract: Objective To investigate the effect of autologous bone marrow mesenchymal stem cells (MSCs) transplantation on cardiac function and their proliferation and differentiation in the post-infarct myocardium in rabbits. Methods Twenty New Zealand rabbits were randomly divided into two groups, the autologous bone marrow mesenchymal stem cells group (MSCs group,n=10) and control group (n=10). Myocardial infarct model was set up by ligation of the left anterior descending (LAD), two weeks after establishment of the infarct model,either 400μl of cell suspension (total cells 1×106) labled by 1,1’-dioctadecyl3,3,3’,3’-tetramethyl indocarbocyanine perchlorate (Dil) or a comparable volume of L-DMEM medium were autologously transplanted into several different points of the periphery of the scar respectively. To evaluate the heart function, echocardiography were performed before modeling,two weeks after modeling, 2 and 4 weeks after the cells transplantation for asurements of left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD), tocalculate left ventricular eject fraction(LVEF) and left ventricular fractional shortening (LVFS). Meanwhile the myocardial contrast echocardiography (MCE) were performed for evaluating the blood perfusion of the post-infarct myocardium. Eight weeks after the transplantation, the animalswere undergoing euthanasia, specimens were acquired for pathology. Results Echocardiography indicated that:The LVEF and LVFS between two groups were fundamentally the same before modeling,two weeks after modeling respectively (0.72±0.08 vs. 0.71±0.04,0.56±0.11 vs. 0.55±0.09; 0.35±0.06 vs. 0.35±0.04, 0.24±0.08 vs. 0.23±0.03, Pgt;0.05), but those were improved significantly in group MSCs when compared with control group at two weeks and four weeks after the cells transplantation(0.71±0.05 vs. 0.60±0.05，0.72±0.07 vs. 0.62±0.08 and 0.34±0.03 vs. 0.29±0.01， 0.35±0.06 vs. 0.27±0.05 respectively,Plt;0.05). There were no differences in LVESD and LVEDD between two groups in any time points(Pgt;0.05). MCE showed the blood perfusion of the infarct myocardium were improved two and four weeks after the cell transplantation. Pathology indicated that Dil positive cells were survived in MSCs transplanted hearts, stained positively for αsarcomeric actin and desmin eight weeks after cell transplantation, HE slides indicated that the capillary density in all the cells transplanted hearts were much higher when compared with control group (38.6±7.6/mm2 vs. 21.4±3.9/mm2，Plt;0.05). ConclusionMSCs can differentiate into cardiomyocytes, improve myocardial perfusion and cardiac function when transplanted into ischemic myocardium.
ObjectiveTo study the external biocompatibility bewteen the mouse induced pluripotent stem cells (miPSCs) and poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx). MethodsAfter we recovered and subcultured miPSCs, we divided them into two groups. There was one group cultured with material of PHBHHx films outside the body. We observed the adhesive pattern of miPSCs on film by fluorescence of 4, 6-diamidino-2-phenylindole (DAPI) staining. The cell vitality was detected by cell counting kit-8 (CCK-8). The morphology of miPSCs attached on the film was visualized under scanning electron microscope (SEM). We used the traditional petri dish to culture miPSCs and detect the cell activity by CCK-8. ResultsMiPSCs can adhere and proliferate on PHBHHx films. The result of cell vitality which detected by CCK-8 showed that there was a statistical difference in OD value between culturing on PHBHHx films and traditional cultivation (0.617±0.019 vs. 0.312±0.004, P < 0.05). ConclusionThere are adhesion and proliferation on the surface of cells patch made by miPSCs co-culturing with PHBHHx film. Compared with traditional culturing in the cell culture dish, culturing in PHBHHx films have great advantages in the process of adhesion and proliferation. PHBHHx can be used as one of the scaffold for stem cells treating various disease.
Objective To review the research progress in cell therapy and tissue engineering approach to regenerate salivary gland so as to provide a theoretical basis for the treatment of salivary hypofunction. Methods The recent literature on cell therapy and tissue engineering for the regeneration of salivary glands was reviewed and summarized. Results It is feasible to repair the salivary function by using various stem cells to repair damaged tissue, or by establishing salivary gland tissueex vivo for salivary gland function restoration and reconstruction. However, the mechanism of three dimensional culturing salivary organoids during organogenesis and function expressing and the potential influence of tissue specific extracellular matrix during this process should be further studied. Conclusion Basic research of cell therapy and salivary tissue engineering should be deeply developed, and a standardized culturing system should be establishedin vitro. In addition, it is of great significance to study thein vivo effects of salivary gland-specific cells, non salivary gland epithelial cells and transplanted gene-transfected stem cells.
【Abstract】 Objective To review the progress and cl inical appl ication of cellular therapy for stress urinaryincontinence (SUI). Methods The l iterature about cellular therapy of SUI was extensively reviewed. Results Becauseof having no or poor regeneration capacity, the cl inical application of chondrocytes and myoblasts were l imited. Based on the rapid progress in stem cell biology, an increasing number of animal experiments and cl inical trials about cellular therapy of SUI have been reported with encouraging results. All these show that cellular therapy has great potential in cl inical application. Stem cells are considered as ideal seeded-cells for treatment of SUI. Conclusion Cellular therapy, especially stem cells, provides a novel approach for treatment of SUI, but the mechanism needs further study.
Objective To review the advance in the experimental studies and evaluate the potential therapeutic application of the mesenchymal stem cells(MSCs). Methods The related articles published in China and theother countries during the recent years were extensively reviewed and analyzed. Results The MSCs were widely used in the cell-transplantation therapy and the tissue engineering because of their pluripotency of differentiation into various kinds of cells. They were also frequently used in the gene therapy because they could stably express the transfected objective genes. Because of their immunomodulatory function, the MSCs could also be used in the immunotherapy. Conclusion The MSCs are the stem cells, which have characteristics of renewing themselves, having multipotency, and being easy to undergo amplification in vitro.The MSCs are ideal target cells for the cell therapy, tissue engineering, gene therapy, and immunotherapy.
Objective To explore repair role of allogeneic bone marrow mesenchymal stem cells （BM-MSCs） transplantation on treating hepatic ischemia reperfusion injury （HIRI） in rats. Methods Ten rats were executed to get BM-MSCs， then BM-MSCs were cultured in vitro and dyed by 4，6-diamidino-2-phenylindole （DAPI）. Models of 70% hepatic ischemia reperfusion injury were eatablished. Thirty two rats were randomly divided into sham operation group （Sham group）， ischemia reperfusion group （I/R group）， Vitamin C group （VC group）， and BM-MSCs group. Serum samples were analyzed for ALT and AST， and hepatic tissue were for superoxide dismutase （SOD） and malondialdehyde （MDA）. Liver sections were stain with hematoxylin and eosin （HE） for histological analysis， TUNEL staining was applied to detect hepatic apoptosis. Serum and tissues were both collected at 24 h after reperfusion. Results The isolated BM-MSCs maintained vigorous growth in vitro. Specific markers for MSCs antigens CD29 and CD44 were detected by flow cytometry， but antigens CD34 and CD45 were not be detected. Models of HIRI were stable， and BM-MSCs were detected around the periportal area by DAPI staining. Compared with I/R group， levels of ALT， AST， MDA， and AI in the VC group and BM-MSCs group decreased at 24 h after reperfusion （P＜0.05）， meanwhile SOD level increased （P＜0.05）. Compared with VC group， levels of ALT， AST， MDA， and AI in the BM-MSC group decreased at 24 h after reperfusion （P＜0.05）， meanwhile SOD level increased （P＜0.05）. Conclusion BM-MSCs could protect HIRI by alleviating oxidative stress and inhibiting cellular apoptosis.