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.
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.
Objective To review the research progress and clinical prospect of three-dimensional spheroid culture of mesenchymal stem cells (MSCs). Methods Recent literature about three-dimensional spheroid culture of MSCs was summarized, mainly on the formation of MSCs spheroids collected by three-dimensional culture, differences between MSCs spheroids and MSCs collected by traditional two-dimensional culture, and the mechanism underlying these differences. Last, its clinical prospect was discussed. Results Compared with MSCs collected by traditional two-dimensional culture, MSCs spheroids collected by three-dimensional culture get a salient up-regulation in anti-apoptosis, multiple differentiation potential, paracrine, and anti-inflammatory effect, which may be related to the morphology and cytoskeleton organization, cell-to-cell contact and gap junctions, and the hypoxia microenvironment. The animal experiments show obvious effects in repair of refractory wounds, repair of ischemic injury, and tissue remodeling, so MSCs spheroid has broad clinical prospect. Conclusion MSCs spheroids collected by three-dimensional culture have stronger biological potential and treatment effect than MSCs collected by traditional two-dimensional culture, MSCs spheroids can be used to optimize stem cell therapy and improve its treatment effect.
With the discovery of cardiac stem cell, the conception of the heart considered to be a terminally differentiated organ was changed. Cardiac stem cells possess the common characteristics of self-renew, clone formation and differentiating into cardiomyocyte, smooth muscle cell, and endothelial cell. Because of the properties of tissue specificity and lineage commitment, cardiac stem cells are considered to have great advantages over other stem cells in the treatment of cardiovascular disease. However, the low rate of engraftment still remains a problem to be solved. In recent years, people attempted to combine stem cell therapy with other ways, such as tissue engineering, gene therapy, exosome therapy, to cure cardiovascular diseases, aiming at finding better ways to treat the cardiovascular disease. This article is mainly for the reviewing of the mechanisms underlying the stem cell therapy and the combinatory use of new technology emerged these years.
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 review the recent research progress of different types of stem cells in the treatment of ischemic stroke.MethodsBy searching the PubMed database, a systematic review had been carried out for the results of applying different types of stem cells in the treatment of ischemic stroke between 2000 and 2020.ResultsStem cells can be transplanted via intracranial, intravascular, cerebrospinal fluid, and intranasal route in the treatment of ischemic stroke. Paracrine and cell replacement are the two major mechanisms of the therapy. The researches have mainly focused on utilization of neural stem cells, embryonic stem cells, and mesenchymal stem cells. Each has its own advantages and disadvantages in terms of capability of migration, survival rate, and safety. Certain stem cell therapies have completed phase one clinical trial.ConclusionStem cells transplantation is feasible and has a great potential for the treatment of ischemic stroke, albeit that certain obstacles, including the selection of stem cells, transplantation strategy, migration ability, survival rate, still wait to be solved.
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.