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BACKGROUND: Abnormal hematopoietic microenvironment is an important factor causing dyshematopoiesis. However, no consensus has been reached on the sensitivity of hematopoietic stromal cells to irradiation.OBJECTIVE: To observe the changes of marrow stromal cells (MSCs) cycle and DNA content during the early stage of irradiation damage in mice, so as to further understand dyshematopoiesis due to radiation and provide scientific basis to avoid deleterious factors in hematopoietic environment.DESIGN: Completely randomized grouping and randomized controlled study based on the experimental animals.SETTING: Central laboratory of altitude military affairs medical department and altitude research institute of preventive medicine department, a military medical university of Chinese PLA.MATERIALS: This study was carried out at the Experimental Animal Center of Third Military Medical University between October 2002 and April 2003. A total of 60 healthy male Kunming mice were randomly divided into irradiation damage group and healthy control group, each having 30 mice.METHODS: The 30 mice in irradiation damage group were exposed to 60Co-γ of irradiation at a dose rate of 1.27 Gy/minutes within a distance of 4 m. Then the mice' marrow cells were harvested at day 3 and day 7 after irradiation, and were cultured in vitro for 14 days and 21 days for observation. Meanwhile the other 30 healthy mice unexposed to irradiation were considered as normal controls.MAIN OUTCOME MEASURES: Post-radiation number of MSCs colonies,cell cycle and DNA content.RESULTS: Although MSCs could grow and be adhered to walls after being exposed to irradiation of 5.0 Gy/s, the number of MSCs colonies was found significantly decreased compared to that of rnormal control group( P < 0.01 ).The colony number of the MSCs irradiated for 7 days obviously increased than that of MSCs irradiated for 3 days; however, MSCs recovered slowly and resulted in prolonged culture time, indicating the inhibited proliferation of MSCs due to irradiation damage. Results of flow cytometry showed that cells in G2+ M phase(2.60±0.41, 4.20±1.27) and DNA content (58.40±0.79,61.17 ± 1.35) in irradiation groups after 3-day and 7-day irradiation were obviously lower than those of normal control group(12.60 ±0. 75, 78.57±0. 83)(P <0.05-0.01).CONCLUSION: MSCs have relatively high sensitivity to irradiation damage and longer persisting period.
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Objective To compare the irradiation-protective and inter-synergestic effects of E838,WR-2721, Rubia cordifolia, cystamin e hydrochloride and ethinyl estradiol on radiation and combined radiation-burn injury. Methods Above-mentioned drugs were given to the mice i ntraperitoneally, or intragastrcally, then, the mortality and the average surviv al d for 30 d were observed before and after the administration of the drug s. Results ①When drugs were before injury , the survival rate and the average survival d of the radiation and combined radiation-burn injured mice were increased obviously with the best effect in E838 and WR-2721. ②When drugs were given after injury, E838 and R. cordifolia also kept the effect. ③Combined appling WR-2721（pre) and E838（post）displayed a significant syner gistic reaction. Conclusion E838 and WR-2721 are more e ffective than the others in the prevention of radiation.
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Objective To observe the repairing effects of myoblasts from mesenchymal stem cells induced by MyoD transfection on muscle injury, and to explore its mechanism. Methods One hundred and sixty male SCID mice were randomly assigned into 4 groups [normal group, control group with injury, implantation with mesenchymal stem cells (MSCs) group, and implantation with myoblasts group]. MSCs were transfected by pIRES2-EGFP-MyoD and differentiated into myoblasts. Myoblasts and MSCs were injected respectively into the muscular tissue injuried by cardiotoxin. The repairing effect in injuried muscles, which were injected with myoblasts and MSCs, was observed 1, 2, 4 and 6 weeks after the injection. Results The muscular tissue injury model was successfully reproduced. Both MSCs and myoblasts showed obvious repairing effects on the injured muscular tissue, and the strength of muscular tissue in myoblasts group was stronger than that in MSCs group. Western blot assay showed that MyoD expression in myoblasts group was much higher than that in both MSCs and control groups, the expressions of JNK1 and ERK2 were up-regulated in myoblasts group, and the p38 expression was down regulated significantly in the 1st week, but no significant difference was found when compared with those of the normal group at the 6th week. Conclusion Myoblasts transdifferentiated from MSCs induced by MyoD can repair the injuried muscular tissue effectively. JNK1, p38 and ERK2 play important roles in the repairing process.
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Besides hematopoietic stem cells, bone marrow also contains another type of stem cells called mesenchymal stem cells (MSCs). With different induced conditions, MSCs have the ability to differentiate into a variety of nonhematopoietic tissue cells, including osteoblasts, chondroblast, adipocytes, myoblasts, astrocytes, and so on. MSCs can be readily obtained from bone marrow by their adhesion to plastic and expansion in culture. Also they can be genetically engineered by transduced target genes. MSCs may be the farget cells for both cell therapy and gene therapy for diseases derived from many different nonhematopoietic tissues.