Bone marrow mesenchymal stem cells protect lungs from smoke inhalation injury by differentiating into alveolar epithelial cells via Notch signaling.

To examine the protective effect of transplanting bone marrow mesenchymal stem cells (BMSCs) in treating lung injuryinduced by smoke exposure and to investigate the underlying mechanisms of this protection. SD rats were randomlydivided into four groups: normal group, normal +BMSCGFP group, smoke group, and smoke +BMSCGFP group. Todetect lung injury, we measured arterial blood gas, the wet-to-dry weight ratio, and levels of interleukin-1b, tumor necrosisfactor-a, interleukin-10, and interleukin-13 in bronchoalveolar lavage fluid and lung tissues. We also conductedhistopathology examinations. The protein markers of alveolar epithelial cells were measured to determine the BMSCdifferentiation. The protein levels of Notch1, Jagged-1, and Hes-1 also were detected. In the present study, BMSCtransplantation significantly decreased the wet-dry weight ratio of the lung, reduced the production of inflammatorymediators, and alleviated lung injury simply through differentiating into alveolar type II cells and alveolar type I cells. Western blot analysis confirmed that the protein expression of Notch-1, Jagged-1, and Hes-1 increased significantly aftersystemic BMSC transplantation. No significant difference was observed between the normal group and the nor-mal +BMSCGFP group. Our findings indicate that systemic transplantation of BMSCs alleviated lung injury induced bysmoke exposure, which may be associated with BMSCs' ability to differentiate into alveolar-type cells via the Notchsignaling pathway.

Inhibitor of DNA-binding 1 promotes endothelial progenitor cell proliferation and migration by suppressing E2-2 through the helix-loop-helix domain.

Vascular endothelial damage is the major contributing factor to cardiovascular diseases. Recently, the therapeutic significance of endothelial progenitor cells (EPCs) has drawn increasing attention due to their roles in re-endothelialization following injury. The inhibitor of DNA-binding 1 (ID1) has been proven to promote EPC proliferation and migration, suggesting a critical function of ID1 in re-endothelialization. However, the underlying mechanisms remain undefined. In this study, ID1 was found to interact with E2-2 using immunoprecipitation analysis. Moreover, ID1 overexpression suppressed E2-2 expression and luciferase reporter activity; however, these effects were not observed in cells transfected with ID1 lacking the helix-loop-helix (HLH) domain (ID1ΔHLH). Further functional analysis corroborated that the upregulation of E2-2 markedly attenuated the ID1-mediated increase in EPC proliferation and migration. Furthermore, the HLH domain plays an important role in ID1-induced EPC proliferation and migration, as its deletion suppressed the positive regulatory effects of ID1 on EPC proliferation and migration. Taken together, the findings of our study confirm that ID1 promotes EPC proliferation and migration by suppressing E2-2 through the HLH domain in ID1. Therefore, ID1 may represent a potential therapeutic target for EPC-mediated re-endothelialization following vascular injury.

Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hindlimb Ischemia through Enhancing Angiogenesis in Tree Shrews.

Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

CCN1 enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia.

Implantation of autologous bone marrow mononuclear cells (BM-MNCs) has been performed in ischemic tissues, for stimulation of angiogenesis, but the limited number of BM-MNCs in patients with hindlimb ischemia disease may offset their overall therapeutic efficacy. CCN1 is a novel and essential regulator during angiogenesis. We evaluated whether CCN1 and BM-MNC are capable of promoting angiogenesis in hindlimb ischemia. In this study, we created the rat model of hindlimb ischemia, and then the rats were randomly divided into four groups: CCN1 infusion plus BM-MNC transplantation (CCN1 + BM-MNCs group), CCN1 infusion plus PBS injection (CCN1 group), vehicle infusion plus BM-MNC transplantation (BM-MNCs group) and vehicle infusion plus PBS injection (control group). The combination of CCN1 and BM-MNC therapy could increase blood perfusion, capillary/muscle fiber ratio and tissue oxygenation in ischemic hindlimb. Moreover, CCN1 could not only inhibit the apoptosis of BM-MNCs, but also enhance the adhesiveness of BM-MNCs to HUVEC. Taken together, CCN1 enhanced angiogenesis of BM-MNC transplantation, and combining CCN1 with BM-MNC transplantation is a useful alternative for ischemic limbs.

[Endovascular therapy for traumatic arterial injury].

OBJECTIVE: To explore the clinical efficacies of endovascular therapy for traumatic arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula. METHODS: From October 2009 to December 2011, 24 patients of arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula underwent endovascular therapy including embolism and stent implantation, etc. RESULTS: Among them, 14 patients were punctured directly and another 10 were punctured after the exposure of arteries. The interventions included embolism (n = 3), embolism plus covered stent implantation (n = 2), covered stent implantation (n = 12) and bare stent implantation (n = 7). And the surgical success rate was 100%. After endoluminal treatment, arterial blood flow recovered, arterial pseudoaneurysm shrank, local pain relieved and venous blood pressure decreased. CONCLUSION: As an effective therapy for traumatic arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula, endovascular therapy has minimal trauma, fewer complications and satisfactory outcomes.

Multiple overlapping bare stents for endovascular visceral aneurysm repair: a potential alternative endovascular strategy to multilayer stents.

BACKGROUND: Multilayer stent has become a new endovascular strategy for visceral artery aneurysm repair. However, its use was not allowed in some areas, such as China. This study evaluates an alternative method: multiple overlapping bare stents for repairing visceral artery aneurysms. METHODS: Twenty-four patients with celiac artery aneurysm (n = 2), splenic artery aneurysm (n = 8), hepatic artery aneurysm (n = 3), superior mesenteric artery aneurysm (n = 6), and renal artery aneurysm (n = 5) were treated with 2 to 4 overlapping bare stents. Long-term results, including clinical achievement ratio and target artery patency, were followed up with computed tomographic angiography. RESULTS: Insertion of overlapping bare stents was successful in all patients. Five aneurysms (21%) were totally excluded 3 months after operation, increasing to 12 (50%) and 20 (83%) aneurysms with total isolation at 6 and 12 months' follow-up, respectively. The clinical achievement ratios of multiple overlapping bare stents on splenic artery aneurysms, hepatic artery aneurysms, renal artery aneurysms, celiac artery aneurysms, and superior mesenteric artery aneurysms were 75%, 100%, 80%, 50%, and 100%, respectively. All cases combined had 100% target artery patency. CONCLUSIONS: Preliminary experience showed that repair using multiple overlapping bare stents seemed to be a potential alternative strategy for treating visceral artery aneurysm, resulting in target artery patency. However, the exact mechanism requires further study and more cases should be involved.

[Clinical treatment of application of deep venous thrombosis by retrievable vena cava filter].

OBJECTIVE: To summarize the clinical experiences of treating deep venous thrombosis (DVT) with retrievable vena cava filter. METHODS: A total of 180 patients with DVT in unilateral lower extremity were recruited. There were 82 males and 98 females with an average age of 46 years old. After the diagnosis of vascular color Doppler ultrasound, retrievable vena cava filter was implanted through contralateral femoral vein. Simultaneously another 114 patients underwent femoral vein embolectomy. All cases received the post-operative therapies of anticoagulation, thrombolysis and vasodilation. RESULTS: The implantation of retrievable vena cava filter was successful in all cases. Among 142 cases of attempted extraction, 116 filters were extracted successfully at Days 12 - 24. The success rate was 81.69%. Filters captured thrombosis in 34 cases (29.31%). CONCLUSION: As a safe and efficacious method, the implantation of retrievable vena cava filter prevents the occurrence of pulmonary embolism in the patients with DVT in unilateral lower extremity. Its timely extraction may avoid the long-term complications.

[Latest cognition of treatment on deep vein thrombosis of lower extremity].

OBJECTIVE: To explore the effects of surgical procedure combined with the intravascular minimal invasive technique for the treatment of deep vein thrombosis (DVT) of lower extremity. METHODS: At the curse of disease from six hours to ninety days, one hundred and two patients with DVT including one hundred and three lower extremities had received surgical procedure and intravascular minimal invasive treatment. RESULTS: There were not procedure-related morbidities in 102 cases, and symptoms disappeared, all procedures were successful based on angiography. The detecting head for the intravascular ultrasound ablation was entered to inferior vena cava (IVC) in 74 cases (78%), Forgarty catheter was entered to IVC in 21 cases (21%), the stenosis in the confluence of the common iliac vein and IVC was dilated by sacculus rotundus catheter in 89 cases (88%), including 9 patients underwent percutaneous transluminal stenting. One hundred and two patients followed up for twenty months, follow-up by angiography showed no restenosis in 91 cases, restenosis in ilio-femoral vein in 1 cases, and thrombus recontouring in 4 cases, as well as 6 cases died caused by primary disease. CONCLUSION: Surgical procedure combined with the intravascular minimal invasive technique is a safe and effective therapeutic method for DVT.