Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction.

BACKGROUND: Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 microg/ml Lipopolysaccharide (LPS) could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 microg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced cardiac protection. METHODS AND RESULTS: Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 microl PBS (control group), 3 x 10(6) wild MSCs/30 microl (wMSCs group), 3 x 10(6) LPS-preconditioned wild MSCs/30 microl (LPS-wMSCs group), or 3 x 10(6) LPS-preconditioned TLR4 gene deleted MSCs/30 microl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs. CONCLUSION: LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs transplantation resulted in superior therapeutic neovascularization and recovery of cardiac function. LPS preconditioning provided a novel strategy in maximizing biologic and functional properties of MSCs.

Treatment with yiqi bushen koufuye combined with chemotherapy for preventing postoperative metastasis of stomach cancer--a clinical observation of 28 cases.

OBJECTIVE: To study the effect of yiqi bushen koufiuye (oral liquid for invigorating qi and tonifying the kidney) combined with chemotherapy on postoperative metastasis of stomach cancer. METHODS: The 47 cases of postoperative stomach cancer with the syndrome of deficiency of both the spleen and kidney were divided randomly into the treatment group (28 cases), and the control group (19 cases). The control group was treated simply by chemotherapy; while the treatment group, was treated with Yiqi Bushen Koufuye in addition to chemotherapy. The effect was observed 12 months later on local relapse and distal metastasis, the life quality, peripheral hemogram, and immunologic function. RESULTS: The rates of postoperative relapse and metastasis of the treatment group were obviously lower than those of the control group (P < 0.05). The Karnofasky scores, peripheral hemogram and immunologic function of the treatment group were obviously improved in comparison with the control group (P < 0.01 or P < 0.05). CONCLUSION: Yiqi bushen koufuye combined with chemotherapy is effective in preventing postoperative metastasis of stomach cancer, increasing sensitivity and decreasing toxins, and improving the life quality and immunologic function of the patient.