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.
Objective To investigate the effects of chondroitinase ABC (ChABC) combined with bone marrow mesenchymal stem cells (BMSCs) in repair spinal cord injury of rats. Methods Primary BMSCs were isolated and cultured from the femur and tibia of neonatal Sprague Dawley (SD) rats. The spinal cord injury model was established in 24 adult SD male rats (weighing, 200-230 g), which were randomly divided into control group (group A), BMSCs transplantation group (group B), ChABC injection group (group C), and ChABC and BMSCs transplantation group (group D), 6 rats in each group. At 7 and 14 days after injury, Basso-Beattie-Bresnahan (BBB) score criteria was used to evaluate the hindlimb motor function; at 14 days after injury, the injured spinal cord tissue was perfused and stained by HE for further calculation of the injury area. Immunofluorescence staining were used for observing the expressions of glial fibrillary acidic protein (GFAP)/chondroitin sulfate proteoglycan (CSPG) and GFAP/growth associated protein 43 (GAP43). Results At 7 days after injury, three joints movement of the hindlimbs were recovered in all groups, and no significant difference in the BBB score was found among 4 groups (P gt; 0.05). At 14 days after injury, no load drag was observed in 3 joints of the hindlimbs in groups A, B, and C, but weight-bearing plantar or occasional dorsalis pedis weight-bearing walking was observed in group D with no plantar walking. The BBB score of group D was significantly higher than that of the other 3 groups (P lt; 0.05). HE staining showed that the cavity formed in the damage zone, and there were a large number of macrophages in the cavity and its surrounding, which was wrapped by scar tissue. The damage area of group D was significantly smaller than that of the other 3 groups (P lt; 0.05). At 14 days after injury, the GFAP/CSPG double immunofluorescence staining showed that the astroglial scar damage zone in group D was significantly reduced, and no cavity formation was found. And the fluorescence intensity in groups C and D was significantly lower than that in group B (P lt; 0.05). The GFAP/GAP43 double immunofluorescence staining showed that GAP43-positive fibers passed through the damage zone in group D and the fluorescence intensity in group D was significantly higher than those in groups B and C (P lt; 0.05). Conclusion Inhibition of astrocytes secreting CSPG by ChABC combined with BMSCs transplantation in early injury may promote the regeneration of nerve fibers, and repair spinal cord injury in rats.
【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 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 review the advances in utilizing paracrine effect of stem cells in knee osteoarthritis (OA) treatment.MethodsThe researches in applying stem cells derived conditioned medium, extracellular matrix, exosomes, and microvesicles in knee OA treatment and cartilage repair were reviewed and analyzed.ResultsThe satisfying outcomes of using different products of stem cells paracrine effect in knee OA condition as well as cartilage defect is revealed in studies in vitro and in vivo. The mechanism including suppressing the intraarticular inflammation, the apoptosis of chondrocytes, and the degradation of cartilage matrix, while enhancing the synthesis of cartilage matrix, the differentiation of in-situ stem cells into chondrocytes and the migration to the affected area. The effectiveness can be further improved supplemented with the tissue engineering methods or gene modification.ConclusionCompared with the traditional stem cell therapy, applying the products from paracrine effect of stem cells in knee OA treatment is more economical and safer, presenting great potential in clinical practice.
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.
Objective To investigate the effect of the serum from severe burn patients on the biology characteristics of human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro, so as to explore the feasibility of hUCMSCs transplantation for treating severe burn. Methods The 3rd passage of hUCMSCs were randomly divided into 3 groups: 10% fetal bovine serum group (group A), 10% normal serum group (group B), and 10% burn serum group (group C). At 24 hours, 72 hours, and 6 days after culture, the cell morphology and density were observed by inverted microscope; the cell proliferation was assessed by MTT; after 6 days of culture, the cell cycle by propidium iodide staining and flow cytometry, the apoptosis by acridine orange/ethidium bromide staining, and the cell senescence by β-galactosidase staining; the levels of tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), platelet-derived growth factor (PDGF), and insulin-like growth factor 1 (IGF-1) in serum were detected by a double-antibody sandwich ELISA kit. Results hUCMSCs were long spindle/polygon in 3 groups. The cell fusion of group C was obviously faster than that in group A and group B. The cell proliferation curves showed that the velocity and number of cell proliferation in group C were significantly higher than those in group A and group B at 2-6 days after culture (P lt; 0.05). The rates of proliferation period (S) of hUCMSCs were 9.21% ± 1.02%, 11.79% ± 1.87%, and 20.54% ± 2.03%, respectively in groups A, B, and C at 6 days, and group C was significantly higher than that of group A and group B (P lt; 0.05). The hUCMSCs showed normal morphology and structure in 3 groups, and no apoptosis cells was observed. The positive cells percentage of group C (2.6% ± 0.1%) was significantly lower than that of group A (4.8% ± 0.2%) and group B (3.8% ± 0.4%) (P lt; 0.05). The levels of TNF-α, IL-1, PDGF, and IGF-1 in group C were significantly higher than those in group B (P lt; 0.05). Conclusion The higher levels of cytokines in serum from the severe burn patients can significantly stimulate hUCMSCs proliferation, prevent cells apoptosis, and reduce cells senescence. Therefore, it is feasible to use hUCMSCs transplantation for treating severe burn patients.
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.