Effects of human umbilical cord mesenchymal stem cells in the treatment of paraquat-induced lung injury / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effect and safety of human umbilical cord mesenchymal stem cells (HUCMSCs) in the treatment of lung injury caused by acute paraquat poisoning.</p><p><b>METHODS</b>Thirteen patients with lung injury caused by acute paraquat poisoning, who were admitted to Guangzhou No. 12 People's Hospital from December 2008 to December 2012, were divided into HUCMSC group (n = 5) and control group (n = 8). All patients received conventional treatment, while the HUCMSC group was treated with HUCMSCs as an addition. Sequential Organ Failure Assessment (SOFA) system, which was created by the Infection Section of European Society of Intensive Care Medicine, and Acute Physiology and Chronic Health Evaluation II were used to acquire the SOFA scores of patients. The lung injury was evaluated with lung injury score (LIS). The two groups were compared with respect to maximum SOFA scores at 1, 3, 5, 7, 14, and 15 days after paraquat poisoning.</p><p><b>RESULTS</b>The HUCMSC group showed significantly lower maximum SOFA scores than the control group at 15d after poisoning (1.80 ± 2.05 vs 13.50 ± 7.59, P < 0.05). The LISs of the HUCMSC group after treatment (0.45 ± 0.27) were significantly lower than those of the HUCMSC group before treatment (1.15 ± 0.34) and those of the control group after treatment (2.94 ± 1.20) (P < 0.01). In the HUCMSC group, all patients survived, and they complained no discomfort and showed normal liver, kidney, and lung functions in reexamination; one patient showed incompletely absorbed shadow in the posterior segment of the left lower lobe of the lung during lung CT scan, and no abnormal findings were seen in other patients. In the control group, one patient survived, and others died. No adverse reactions, such as chill and fever, were presented in the HUCMSC group.</p><p><b>CONCLUSION</b>HUCMSCs show promise for clinical application in the treatment of lung injury caused by acute paraquat poisoning.</p>

Hepatocyte growth factor combined with autologous bone marrow mesenchymal stem cell transplantation for treatment of silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the potential role of hepatocyte growth factor (HGF) combined with bone marrow mesenchymal stem cells (BMSC) autograft for the treatment of silicosis.</p><p><b>METHODS</b>Bone marrow (100 ml) was aspirated from a severe silicosis patient. BMSCs isolated, purified and cultured in vitro. When BMSC came to 70% confluence at passage 3, the culture medium was added liposomes (lipo2000) and plasmid-HGF (p-HGF) and cultured for 2 d. HGF-MSCSs (5 × 10(7) cells) were resuspended in 50 ml 0.9% sodium chloride (NS) and infused Intravenous drip at 3 consecutive times (once a week). Clinical follow-up were performed before and after treatment: (1) pulmonary high-kV X-ray, chest CT examination; (2) pulmonary function test; (3) determination of serum ceruloplasmin.</p><p><b>RESULTS</b>The symptoms such as coughing, chest tightness disappeared at 12 months after treatment. Pulmonary function tests showed significant changes after treatment: forced vital capacity (FVC) increased from 64.6% to 81.0%, forced expiratory volume in one second (FEV(1.0)) increased from 68.7% to 90.1%, 1 second rate (FEV(1.0)/FVC%) reduced from 111.6% to 107.1%, the maximum mid-expiratory flow (FEF(25%∼75%) decreased from 100.2% to 94.6%, forced expiratory vital capacity 75% of the moment bit of gas flow (MEF(75%)) increased from 99.2% to 113.5%, forced expiratory vital capacity 50% of the moment bit of gas flow (MEF(50%)) increased from 125.3% to 130.2%, forced expiratory vital capacity 25% of the moment bit of gas flow (MEF(25%)) reduced from 86.9% to 71.7%; serum ceruloplasmin levels decreased from 690 mg/L to 180.6 mg/L; lung high-kV X-ray at 1st review showed that diffuse lung nodules had been absorbed and getting smaller than before treatment; chest CT showed that the distribution and number of small nodules at double lung fields decreased than before treatment.</p><p><b>CONCLUSION</b>HGF combined with BMSC transplantation may have some potential role for the treatment of silicosis patients.</p>

The experimental study of suppressing silicosis fibrosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To compare the difference of effects on SiO(2)-induced alveolitis and early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs) and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this effects.</p><p><b>METHODS</b>The Primary BM-MSCs from Wistar male young rats were cultured and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were randomly divided into 3 groups:model group (10 rats),which was administered with SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On the 14th and 28th days after treatment, half of the animals were sacrificed, respectively, and the lungs were harvested for frozen section to observe the cell marked by DAPI. HE staining under a fluorescent microscope, and to observe the pulmonary alveolitis and fibrosis by HE and Masson staining under a light microscope. Western blot assay was used to detect the expression of HGF in rat lungs. The expression levels of tumor necrosis factor-α (TNF-α) in pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in pulmonary tissues were analyzed quantitatively by sample hydrolysis method.</p><p><b>RESULTS</b>On the 14th and 28th days after treatment, the scores of pulmonary alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 ± 0.17, 2.8 ± 0.14 and 0.1 ± 0.11, 1.16 ± 0.13, which were significantly lower than those (1.68 ± 0.17, 1.58 ± 0.31 and 0.54 ± 0.15, 1.36 ± 0.13) in BM-MSCs group, also which were significantly lower those (2.36 ± 0.17, 2.80 ± 0.14 and 0.64 ± 0.09, 1.84 ± 0.17) in model group (P < 0.05); On the 14th and 28th days after treatment, the TNF-α contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 280.4 ± 23.11 and 249.78 ± 22.33 pg/mg, which were significantly lower than those (341.58 ± 35.34, 442.29 ± 36.76 pg/mg and 319.51 ± 17.84, 348.53 ± 33.95 pg/mg) in BM-MSCs and model groups (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 ± 0.04 and 0.65 ± 0.05 µg/mg, which were significantly lower than those (0.63 ± 0.04, 1.04 ± 0.07 µg/mg and 0.72 ± 0.60, 1.39 ± 0.60 µg/mg) in BM-MSCs and model groups (P < 0.05).</p><p><b>CONCLUSION</b>The effects of BM-MSCs transfected by pcDNA3.1-HGF on suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary inflammation.</p>

Investigating the treatment of silicosis with autologous bone marrow-derived mesenchymal stem cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the safety and curative effects of autologous bone marrow-derived mesenchymal stem cells (BMSCs) in the treatment of silicosis.</p><p><b>METHODS</b>The protocol was approved by the Ethics Committee of the hospital, and ten patients with silicosis who had given written consent were enrolled in this study. BMSCs isolated from 100 ml of bone marrow for each case were purified and cultured. In each case the 3rd generation of qualified BMSCs (5 × 10(7)) were intravenously administered weekly for 3 weeks. Three cases among 10 patients were treated with BMSCs modified by hepatocyte growth factor (HGF) gene. The clinical symptoms, chest films, chest CT, pulmonary functions, T cells, serum IgG and ceruloplasmin (CP) were observed in 6 or 9 months after treatment.</p><p><b>RESULTS</b>No obvious sub-effect was observed in cases treated with BMSCs, the clinical symptoms (such as cough, sputum and chest tightness) basically disappeared in 9 months after treatment. Pulmonary function tests showed that FVC increased from 71.2% ± 17.0% to 84.0% ± 10.9% (P < 0.01) and FEV1.0 increased from 67.5% ± 17.7% to 80.6% ± 14.9% (P < 0.01). The levels of serum CP and IgG significantly decreased (P < 0.01). Further, the chest films and CT in cases treated with autologous BMSCs modified by HGF gene were improved to different extent.</p><p><b>CONCLUSION</b>Treatment with autologous BMSCs modified by HGF gene exhibit a beneficial effect on silicosis.</p>