Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art.

The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.

Long-term outcomes of combined transarterial chemoembolization and radiofrequency ablation versus RFA monotherapy for single hepatocellular carcinoma ≤3 cm: emphasis on local tumor progression.

PURPOSE: To compare the long-term outcomes of combined transarterial chemoembolization and radiofrequency ablation (TACE-RFA) with radiofrequency ablation (RFA) monotherapy for small (≤3 cm) hepatocellular carcinomas (HCCs). METHODS: A total of 248 patients with 329 HCC nodules who underwent TACE-RFA or RFA monotherapy as the only first-line treatment between January 2009 and December 2020 were included in this study. The technical success, complications, survival rate, and local tumor progression (LTP) rate were compared between the two treatments. RESULTS: The 1-, 3- and 5-year survival rates were similar between the two groups (98.7%, 93.0% and 75.9% vs 97.4%, 88.0% and 77.4%; p = 0.444). The 1-, 3-, and 5-year cumulative LTP rates were significantly lower in the TACE-RFA group than in the RFA monotherapy group (2.9%, 9.2%, and 13.8% vs. 5.2%, 17.0%, and 21.0%; p = 0.043). Subgroup analyses suggested that TACE-RFA showed significantly lower LTP rates than RFA monotherapy for small HCC with tumor size>2cm (p = 0.008), subphrenic location (p = 0.021), and perivessel (p = 0.030). Furthermore, HCC with well-defined lipiodol deposition in the TACE-RFA group showed better local tumor control than the small HCC in the RFA monotherapy group (p = 0.013). There was no significant difference in the technical success rates (p = 0.064) and complication rates (p = 0.952) between the two groups. CONCLUSIONS: TACE-RFA is superior to RFA monotherapy in providing local tumor control for small HCC with tumor size 2-3 cm in diameter, subphrenic location, perivessel and HCCs with well-defined lipiodol deposition by TACE before RFA.

Prognostic Value of HLA Class I in Patients with Hepatocellular Carcinoma.

BACKGROUND: Downregulation of HLA class I molecules is a major tumor escape mechanism from immune attack. However, its prognostic impact for patients with hepatocellular carcinoma is still unclear. This study aimed to investigate whether HLA class I has prognostic significance in patients with hepatocellular carcinoma. METHODS: A cohort of 132 patients with hepatocellular carcinoma was enrolled. HLA class I expression was detected by immunohistochemistry. Levels of HLA class I expression were dichotomized as low and high according to staining intensity or staining percentage of positive tumor cells, respectively. Association of HLA class I expression with clinical characteristics and survival was analyzed. RESULTS: None of the clinical characteristics, including gender, age, virus infection, cirrhosis, AFP, vascular invasion, tumor size and number, was significantly associated with staining percentage of HLA class I or staining intensity (p > 0.05). Low staining percentage of HLA class I was significantly associated with a worse survival (p = 0.011), which was further confirmed by Cox regression hazards model in multivariate analysis (HR 0.416, 95% CI 0.204 - 0.849, p = 0.016). Staining intensity of HLA class I was not significantly associated with survival (p > 0.05). CONCLUSIONS: Expression of HLA class I might be a significant prognostic factor in hepatocellular carcinoma, and downregulation of HLA class I was significantly associated with a worse survival in terms of expression percentage of HLA class I.

Strontium gluconate potently promotes osteoblast development and restores bone formation in glucocorticoid-induced osteoporosis rats.

Glucocorticoid-induced osteoporosis (GIOP) has emerged as a challenge after long-term glucocorticoid administration during the clinical therapy of diverse diseases. Although some candidates for GIOP treatment have been explored, there is still a lack of reliable drugs for GIOP prevention. In this study, rat bone marrow stem cells (rBMSCs) were utilized to investigate the feasibility of applying strontium gluconate (GluSr), which displays mild activity, easy absorption and good biocompatibility, for GIOP prevention. Thirty-two SD rats were divided into 4 groups to explore the effects of GluSr on osteoporosis rescue in vivo. Our results suggested that GluSr markedly alleviated dexamethasone (DEX)-induced apoptosis of osteoblast precursor cells and rBMSCs and enhanced rBMSC osteogenesis differentiation in vitro. GluSr also effectively promoted osteoblast survival, inhibited osteoclast differentiation and restored bone formation in GIOP rat models. Microarray analysis of the femora from GIOP rats treated with GluSr revealed that the signalling pathways of the glucocorticoid receptor (GR), oestrogen receptor gene (ESR) and vitamin D receptor (VDR) were involved in bone restoration by GluSr. In summary, our study proved that GluSr enhanced osteoblast differentiation and suppressed osteoclast activity both in vitro and in vivo. GluSr might function as a novel strontium reagent for GIOP prevention.

Regorafenib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: a real-world study.

BACKGROUND: The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment. METHODS: This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5-7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed. RESULTS: The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1-13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively. CONCLUSIONS: The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.

Safety and Efficacy of Stent Graft Implantation for Malignant Superior Vena Cava Syndrome.

BACKGROUND: Patients with malignant superior vena cava syndrome (SVCS) usually require urgent treatments due to a high potential risk of early mortality. Stent implantation can rapidly improve the symptoms of SVCS, which may be beneficial to subsequent anti-tumor therapy. The aim of the study was to evaluate the clinical outcomes of stent graft implantation for the treatment of superior vena cava (SVC) obstruction caused by non-small cell lung carcinoma (NSCLC) with acute post-stenting occlusion. METHODS: Between October 2014 and December 2019, 16 patients were selected for stent graft implantation. Technical success and clinical efficacy were assessed. Stent patency and patient survival rates, as well as the complications were analyzed. RESULTS: There were 17 stent grafts implanted in 16 patients. The technical success was 100%. The residual stenosis after initial implantation was 64.0 ± 9.0%. The stent expanded to an optimal size in 5.5 ± 2.2 days after the initial deployment. Migration occurred when deploying of the stent graft in one patient; this stent graft was successfully stabilized by a second one. No other complications related to the procedure were found except one migration. At 1, 3, 6, 9 and 12 months, the cumulative survival rates were 100%, 75%, 56%, 19% and 0%, respectively. The mean OS was 173 days. The median survival was 166 days. CONCLUSIONS: Stent graft can be safely used in patients with SVC obstruction with a good long-term patency rate.

RNA-Seq Based Transcriptome Analysis of Endothelial Differentiation of Bone Marrow Mesenchymal Stem Cells.

OBJECTIVE: The aim was to identify the change in gene expression between mesenchymal stem cells (MSCs) and induced endothelial cells (ECs) and to investigate the potential mechanism of endothelial differentiation based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: MSCs were isolated from bone marrow and exposed to inducing medium. The dynamic transcription profiles of MSCs were identified and ECs were induced through RNA-seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signalling pathways analysis were performed based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate the genes selected from RNA-Seq. RESULTS: In total, 2769 DEGs were identified, of which 1117 genes were upregulated and 1652 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including extracellular matrix organisation, blood vessel morphogenesis, angiogenesis, extracellular matrix binding, growth factor binding and glycosaminoglycan binding extracellular matrix-receptor interaction pathway, cytokine-receptor interaction pathway and transforming growth factor (TGF)-ß signalling pathway. All genes found to be associated with the TGF-ß pathway were significantly downregulated. Eleven novel genes were also identified that most likely are involved in endothelial differentiation and were upregulated with more than 10 fold change, which were further validated by qRT-PCR. CONCLUSION: The GO and KEGG analysis revealed that extracellular matrix, cytokines and the TGF-ß pathway play an important role in the process of endothelial differentiation. Furthermore, 11 genes were found that may be involved in the differentiation of MSCs into ECs and contribute to current understanding of the differentiation mechanism.

Spontaneous rupture of enormous renal angiomyolipoma in a pregnant tuberous sclerosis patient: a rare case.

BACKGROUND: Renal angiomyolipoma (RAML) is a rare benign kidney tumour comprised of adipose tissue, smooth muscle, and blood vessels. It can cause fatal complications if it ruptures. Although there have been reports of RAMLs rupturing, it is unusual to see RAMLs rupture during pregnancy, especially in pregnant women with tuberous sclerosis (TSC). Moreover, we reported a rare complication after selective arterial embolization (SAE) for the first time, which called aseptic liquefaction necrosis. CASE PRESENTATION: The case is a 16-week-pregnant woman with TSC who presented with severe flank pain, which was secondary to the rupture of a large, previously unknown RAML. This was confirmed by emergency computed tomography and successfully treated with selective arterial embolization after the patient received counselling and provided prior informed written consent for medical termination of pregnancy (MTP). The patient underwent abortion 3 weeks after the SAE. The patient required drainage 2 months after the SAE because of aseptic liquefaction necrosis. During follow-up, the patient's lesion remained stable. CONCLUSION: RAML rupture is a rare but rather serious complication in pregnant tuberous sclerosis patients. Selective arterial embolization (SAE) should be performed immediately, and the status of the pregnancy needs to be assessed by a multidisciplinary team. We also report for the first time the rare complication of aseptic liquefaction necrosis after SAE of RAML, for which percutaneous drainage is effective.

Comparison of blood oxygen level-dependent imaging and diffusion-weighted imaging in early diagnosis of acute kidney injury in animal models.

BACKGROUND: Early diagnosis of acute kidney injury (AKI) has clinical importance. Current methods are neither adequately sensitive nor specific. Blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) may help to assess AKI in the early phase. PURPOSE: To investigate the feasibility of BOLD imaging and DWI in the assessment of AKI and compare the sensitivities of both techniques in early detection of renal damage. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Thirty New Zealand white rabbits. FIELD STRENGTH/SEQUENCE: 3 T clinical MRI/BOLD and DWI. ASSESSMENT: Thirty rabbits were divided into three groups (severe AKI group, mild AKI group, and control group). Transarterial renal embolization with different doses of microspheres was performed to create severe and mild AKI disease models. All the MRI scans of kidneys were conducted within 2 hours after the embolization procedure. Histological examinations with hematoxylin and eosin staining were performed to validate renal damage. STATISTICAL TESTS: Analysis of variance (ANOVA) for comparisons between groups, and paired t-test for tests within the same group. P < 0.05 was considered statistically significant. RESULTS: Both R2* and apparent diffusion coefficient (ADC) showed significant differences between the severe AKI group (56.34 ± 3.45 s-1 for R2*, 1.14 ± 0.23 mm2 /s for ADC) and the control group (28.24 ± 2.26 s-1 for R2*, 1.94 ± 0.33 mm2 /s for ADC, both P < 0.01). However, the ADC values did not show significant differences (P = 0.41) between mild AKI group (1.88 ± 0.31 mm2 /s for ADC) and the control group (1.94 ± 0.33 mm2 /s for ADC), while R2* was still useful in differentiating the two groups (52.32 ± 4.1 s-1 vs. 28.24 ± 2.26 s-1 for R2*, P < 0.01). The histopathologic results were found to be correlated with MRI findings. DATA CONCLUSION: BOLD contrast and DW images are both effective in detecting AKI noninvasively, but BOLD imaging is more sensitive in early detection of mild ischemia than DWI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:719-724.

IN.PACT SFA Clinical Study Using the IN.PACT Admiral Drug-Coated Balloon in a Chinese Patient Population.

Purpose: To confirm the safety and effectiveness of the IN.PACT Admiral drug-coated balloon (DCB) as a treatment for de novo and native artery restenotic lesions in the superficial femoral artery (SFA) and/or proximal popliteal artery in Chinese subjects. Materials and Methods: IN.PACT SFA China (ClinicalTrials.gov identifier NCT02118532) was a single-arm, independently adjudicated, prospective, premarket study that enrolled 143 subjects (mean age 66.8±7.7 years; 107 men) at 15 centers. The predominant risk factors were hypertension (104, 72.7%) and diabetes mellitus (66, 46.2%). The majority of subjects were classified as Rutherford category 2 or 3 [69 (48.3%) and 55 (38.5%), respectively]; 19 (13.3%) subjects had critical limb ischemia (Rutherford category 4). The mean lesion length was 10.4±6.51 cm; more than half of the lesions (75, 52.4%) were chronic total occlusions. Calcification was found in 66 (46.2%) lesions. Outcomes at 12 months were compared with DCB safety and effectiveness performance goals derived from the literature. The 30-day primary safety outcome was a composite of freedom from device- and procedure-related mortality, major target limb amputation, and clinically-driven target lesion revascularization (CD-TLR). Results: The primary safety outcome was 99.3% at 30 days. Follow-up compliance at 12 months was 92.6%. Estimated 1-year primary patency using Kaplan-Meier analysis was 90.9% and freedom from CD-TLR was 97.1%. The rate of CD-TLR at 12 months was 2.9%. The Rutherford category status improved significantly (p<0.001) between baseline and 12 months. Conclusion: Results from IN.PACT SFA China demonstrated high rates of patency and low rates of CD-TLR in Chinese subjects through 12 months despite patient and lesion complexity. These data are consistent with the results of other IN.PACT DCB trials.

Prognostic Value of PD-L1 in Patients with Hepatocellular Carcinoma.

BACKGROUND: The aim of the study is to investigate whether programmed death ligand l (PD-L1) on tumor cells has prognostic significance in patients with hepatocellular carcinoma. METHODS: A cohort of 143 patients with hepatocellular carcinoma was enrolled. PD-L1 expression was detected by immunohistochemistry. The association of PD-L1 expression with clinical characteristics and survival was analyzed. RESULTS: PD-L1 positive rate in our study was 13.3% (19/143). None of clinical characteristics, including gender, age, virus infection, AFP, vascular invasion, tumor size, and number, was significantly associated with PD-L1 expression (p > 0.05). PD-L1 expression was significantly associated with cirrhosis (p = 0.016). PD-L1 expression was not significantly associated with survival (Log-rank p = 0.076; HR: 0.363 p = 0.091). CONCLUSIONS: PD-L1 expression failed to have a markedly significant prognostic association with survival in patients with hepatocellular carcinoma.

Cerebral Hemodynamic Variations in the Early Stage after Carotid Artery Stenting in Patients with and without Near Occlusion.

BACKGROUND: To evaluate the unclear cerebral hemodynamic variations in patients with and without near occlusion (NO) in hours after carotid artery stenting (CAS) by transcranial Doppler (TCD). METHODS: Data of 56 patients (11 patients with carotid artery NO and 45 patients with severe stenosis without NO) who underwent unilateral CAS were analyzed. All patients underwent TCD or transcranial color-code Doppler monitoring before CAS and again at one and three hours after the procedure. We compared bilateral middle cerebral artery peak systolic velocity (MCA-PSV), pulsatility index (PI), and blood pressure (BP) data between the two groups. RESULTS: Ipsilateral MCA-PSV increased relative to baseline in the stenosis group at one hour (97 ± 30 vs. 84 ± 23 cm/s, 16%, P < 0.001) and three hours (96 ± 28 vs. 84 ± 23 cm/s, 15%, P < 0.001) after CAS. Corresponding increases were distinctly higher in the NO group than in the stenosis group at one hour (116 ± 37 vs. 80 ± 29 cm/s, 51%, P < 0.001) and three hours (113 ± 39 vs. 80 ± 29 cm/s, 46%, P = 0.001) after CAS, whereas BP decreased similarly between the two groups. The ipsilateral PI increased postsurgically in both groups, whereas contralateral MCA-PSV was unaltered. CONCLUSIONS: CAS can induce a significant increase in PSV and PI in ipsilateral MCA within three hours in patients with NO or severe stenosis but absent NO. The increment of ipsilateral MCA-PSV was greater in patients with NO. TCD can facilitate BP control in the early stage after CAS in patients with NO.

Quality of Life, Adverse Events, and Reintervention Outcomes after Laparoscopic Radiofrequency Ablation for Symptomatic Uterine Fibroids: A Meta-Analysis.

In this review, we assessed the short-term (3 and 6 months) and long-term (12, 24, and 36 months) symptom relief and quality of life improvement, procedure-related adverse event rate, reintervention rate, and days missed from work after laparoscopic radiofrequency ablation. Using MeSH keywords "uterine fibroid" and "ablation technique," a systematic search was performed in PubMed, Ovid, Embase, Cochrane Library, and Clinicaltrials.gov. Studies consisting of uterine fibroid symptoms and quality of life scores were considered eligible. Both comparative and noncomparative studies were included. Using a random-effects model, a meta-analysis was performed. Eight studies with a total of 581 patients were finally included in our review. Based on validated questionnaires, quality of life improved significantly until 36 months after laparoscopic radiofrequency ablation therapy, with a maximum improvement (Health-Related Quality of Life [HRQL] questionnaire score of +41.64 [95% confidence interval (CI), 38.94-44.34] and a transformed Symptom Severity Score [tSSS] of -39.37 [95% CI, 34.70-44.04]) at 12 months after laparoscopic radiofrequency ablation. All subscales of quality of life improved significantly, and most of the changes remained stable in long-term follow-up. The overall reintervention rate was 4.39% (95% CI, 1.60%-8.45%), and the median uterine volume reduction was 69.17 cm³ (95% CI, 35.87-102.46 cm³).The overall procedure-related adverse events rate was 1.78% (95% CI, 0.62%-3.53%), and patients missed an average of 4.35 days (95% CI, 2.55-6.15 days) of work. In conclusion, laparoscopic radiofrequency ablation therapy is an efficacious way to treat small-sized and nonpedunculated symptomatic uterine fibroids, providing stable long-term symptom relief and quality of life improvement with a low risk of adverse events and reintervention and just a few days of missed work.

Efficacy and safety of preoperative internal maxillary arterial embolization with gelfoam for nasopharyngeal angiofibroma.

PURPOSE: To investigate the efficacy and safety of preoperative internal maxillary arterial embolization with gelfoam particles in patients with nasopharyngeal angiofibroma. MATERIALS AND METHODS: We retrospectively reviewed a total of 27 consecutive patients with pathologically confirmed nasopharyngeal angiofibroma from August 2006 to September 2018. Of the 27 enrolled patients, 10 patients received surgical excision alone; 17 patients received preoperative internal maxillary arterial embolization followed by surgical excision. Embolic agents were gelfoam particles. RESULTS: The mean volume of intro-operative blood loss was 385.3 ml in patients with preoperative arterial embolization, which was significantly lower than 1215.0 ml in the patients without preoperative arterial embolization (P < 0.001). The mean surgical time was shorter in patients with preoperative arterial embolization than in the patient without preoperative arterial embolization, but the difference had no statistical significance (205.0 vs 264.5 min, P = 0.064). Neurological complications such as facial palsy or vision loss or hemiplegia were not observed in patients with preoperative arterial embolization. CONCLUSION: Internal maxillary artery embolization with gelfoam particles suffices to provide an effective and safe adjuvant procedure for surgical excision of nasopharyngeal angiofibroma.

Anti-apoptosis endothelial cell-secreted microRNA-195-5p promotes pulmonary arterial smooth muscle cell proliferation and migration in pulmonary arterial hypertension.

In the pathological mechanism of pulmonary arterial hypertension, the role of apoptosis-resistant pulmonary microvascular endothelial cells (PVECs/AR) has been emphasized on the pulmonary vascular remodeling. In the present study, we investigated whether PVECs/AR can promote the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), and to study the role of miR-195-5p in the crosstalk between these two types of cells. We confirmed that PVECs/AR can promote the proliferation and migration of PASMCs in a co-culture system of AR/PVECs and PASMCs. Additionally, after exposure to hypoxia for 12 or 24 h, AR/PVECs had a higher mature miR-195-5p level than PVECs (P < 0.05, 12 and 24 h). Luciferase reporter assays were used to validate indications of the existence of an HRE in the miR-195-5p promoter. Knocking down Smad7 can reverse the inhibition of Lv-S195 on TGF-ß1-induced PASMCs remodeling. TGF-ß1 promoted cell growth in PASMCs, and the supernatant of PVECs/AP infected with Lv-S195 inhibited TGF-ß1 enhanced proliferation in PASMCs, which was also blocked by Lv-shRNA-Smad7. The result of this experiment confirmed the specificity of the HIF-1a/miR-195/Smad7 pathway. Our data indicate the possible function of PVECs/AR in the process of pulmonary vascular remodeling. MiRNA-195-5p played a role as an interacting paracrine factor between PVECs/AR and PASMC, which seemed to function through the HIF-1a/miRNA-195-5p/Smad7 pathway.

Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial Cells in Vitro.

OBJECTIVE: Endothelial cells (ECs) play an important role in neovascularisation, but are too limited in number for adequate therapeutic applications. Mesenchymal stem cells (MSCs) have the potential to differentiate into endothelial lineage cells, which makes them attractive candidates for therapeutic angiogenesis. The aim of this study was to investigate efficient differentiation of MSCs into ECs by inducing medium in vitro. METHODS: MSCs were isolated from bone marrow by density gradient centrifugation. The characterisation of the MSCs was determined by their cluster of differentiation (CD) marker profile. Inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied to differentiate the MSCs into ECs. Endothelial differentiation was quantitatively evaluated using flow cytometry. Real time quantitative PCR (qRT-PCR) was used to analyse mRNA expression of endothelial markers. Tube formation assay was further performed to examine the functional status of the differentiated MSCs. RESULTS: Flow cytometry analysis demonstrated that CD31+ and CD34+ cells increased steadily from 12% at 3 days, to 40% at 7 days, and to 60% at 14 days. Immunofluorescence staining further confirmed the expression of CD31 and CD34. qRT-PCR showed that expression of von Willebrand factor (vWF), vascular endothelial cadherin (VE-cadherin) and vascular endothelial growth factor receptor-2 (VEGFR-2) were significantly higher in the induced MSCs group compared with the uninduced MSCs group. The functional behavior of the differentiated cells was tested by tube formation assay in vitro on matrigel. Induced MSCs were capable of developing capillary networks, and progressive formation of vessel like structures was associated with increased EC population. CONCLUSIONS: These results provide a method to efficiently promote differentiation of MSCs into ECs in vitro for potential application in the treatment of peripheral arterial disease.