Transduction of mesenchymal stem cells with multidrug resistance gene provides protection for bone marrow toxicity after being transplanted into a nude mice model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdr1) gene is well-known for its ability to confering drug resistance. In this study, we meant to transplant the placenta mesenchymal stem cells (P-MSCs) moderated by mdr1 gene into a nude mice model radiated by γ-Co(60) and to explore the chemoprotection for bone marrow (BM) toxicity.</p><p><b>METHODS</b>Human P-MSCs were isolated from trypsin-digested term placentas and then transduced by with reconstructed retroviral vector containing mdr1 gene and green fluorescent protein (GFP) reporter gene. The integration and expression of mdr1 gene was observed indirectedly by the expression of GFP. A nude mice model was constructed after irradiation with a sublethal dosage of γ-Co(60). These irradiated mice were transplanted with mdr1-MSCs through the caudal vein and then received paclitaxel (PAC) intraperitoneal chemotherapy. The Peripheral peripheral blood (PB) of the nude mice was collected, and the PB cells counts and values were determined using an automatic analyzer.</p><p><b>RESULTS</b>After PAC treatment, mdr1-MSCs transplanted mice showed markedly improved survival upon compared to MSCs transplanted mice (85.7% vs. 57.1%). White blood cell (WBC) and red blood cell (RBC) counts as well as the hemoglobin (Hb) values were significantly increased in PAC treated mdr1-MSCs mice compared to PAC treated control mice when PAC chemotherapy had been finished (all P < 0.05), but the difference was not found in the plateltes (PLT) count (P > 0.05).</p><p><b>CONCLUSION</b>Human P-MSCs moderated by mdr1 gene when transplanted into nude mice may provide chemoprotection for hematopoietic toxicity.</p>

Advance in animal models of traumatic brain injury / 法医学杂志

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Animal models of TBI are used to elucidate primary and secondary injury mechanisms and pathophysiological changes and to provide the diagnostic and therapeutical basis for TBI. The choices of animal models depend upon the research objectives. However, various animal models have limitations. The models only can duplicate the pivotal injury mechanisms or a certain important pathophysiological course. The characteristics of human TBI can not fully be reflected by using these models. In the review, animal models of traumatic brain injury are classified as dynamic direct brain injury, indirect dynamic brain injury and combined neuro-traumatic models. Several common models are described for consideration.

Effect of intra-articular ozone injection on serum and synovial TNF-α, TNFR I, and TNFR II contents in rats with rheumatoid arthritis / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of intra-articular ozone injection at different concentrations on the contents of tumor necrosis factor-α (TNF-α), TNF receptor I (TNFR I), and TNFR II in the serum and synovium of rats with rheumatoid arthritis (RA) and explore the therapeutic mechanism of ozone in RA treatment.</p><p><b>METHODS</b>Forty-eight Wistar rats were randomized into 8 groups, including 5 ozone groups receiving intra-articular injection of 10, 20, 30, 40 or 50 µg/ml ozone, a blank control group, an oxygen group and a RA model group. All the rats, except for those in the blank control group, were subjected to hypodermic injection of bovine collagen II and complete Freunds adjuvant to induce RA. Ozone treatment was administered once weekly for 3 weeks starting at 21 days after the modeling. The swelling and thickness of the hind paws were observed, and the serum and synovial contents of TNF-α, TNFR I, and TNFR II were detected.</p><p><b>RESULTS</b>At the end of treatment, the paw thickness was reduced significantly in rats with 40 µg/ml ozone injection compared with that in the model RA group (P<0.01). The serum contents of TNF-α, TNFR I and TNFR II showed no significant difference between the RA model group, oxygen group and the ozone groups, but their synovial contents showed significant reductions in rats with 40 and 50 µg/ml ozone injection (P<0.01); the synovial TNFR I was significantly higher in 40 µg/ml ozone group than in the model group (P<0.05).</p><p><b>CONCLUSION</b>Intra-articular injection of 40 µg/ml ozone can attenuate synovitis in rats with RA, the mechanism of which may involve the inhibition of TNF-α and TNFR II activity and enhancement of TNFR I activity in the synovium.</p>

Effect of ozone water on the inflammation and repair in infected wounds / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of ozone water in promoting the healing of infected wounds.</p><p><b>METHODS</b>Fifty Wistar rats were randomly divided into 5 groups, namely chlorhexidine treatment group, 5, 10, and 20 mg/L ozone water treatment groups, and the control group without any treatment. Infected wounds were induced on the back of the rats, and at 48 h of infection, chlorhexidine or ozone water was applied once daily for 9 days. Before and at days 3, 6, and 9 of the treatment, the wound changes were observed. The WBC in the tail venous blood was detected and the incised skin and muscular tissues were pathologically examined. RESULTS AMD CONCLUSION: Ozone water showed better effects in promoting the healing of the infected wound, especially at higher doses of 10 and 20 mg/L.</p>

Retroviral-mediated transfer and functional expression of multidrug resistance gene in human placenta mesenchymal stem cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Most of gynecologic malignancies are sensitive to chemotherapy. Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdr1) gene is well known for its ability to confer drug resistance. This study aimed to explore the feasibility of expression and resistance of mdr1 gene transduction into human placenta mesenchymal stem cells (P-MSCs) by retrovirus vector.</p><p><b>METHODS</b>Human P-MSCs were isolated from trypsin-digested term placentas, and their immunophenotypes and differentiation potential were evaluated. Human P-MSCs were transduced by reconstructed retroviral vector containing the mdr1 gene and green fluorescent protein (GFP) reporter gene. The integration and expression of the mdr1 gene were observed indirectly by the expression of GFP, and fluorescence-activated cell sorter was used to evaluate the functional activity of permeability glycoprotein (P-gp) encoded by the mdr1 gene. The stimulating test was made in vitro to show pleiotropic drug resistance of transfected cells.</p><p><b>RESULTS</b>The isolated, cultured and expanded P-MSCs expressed stem cell markers such as CD29, CD44 and CD73, and showed osteogenic and adipogenic differentiation potentials under appropriate conditions. The expression of P-gp in the non-transfected P-MSCs cells was (0.4 +/- 0.1)%, but increased to (28.1 +/- 4.7)% after gene transfection (P < 0.01). And positive staining of P-gp located mainly at cell membrane and cytoplasm. Accumulation and extrusion assays showed that P-gp expressed by the transfected cells had pump-functional activity and could efflux daunomycin out of cells. The analysis of cell survival confirmed that transfected P-MSCs had a characteristic of multidrug resistance with a significant increase in the resistance to anticancer agents.</p><p><b>CONCLUSIONS</b>Transfer and expression of human mdr1 gene mediated by retrovirus vector conferred P-MSCs drug resistance. It might provide a new alternative to chemoprotection strategies.</p>