Percutaneous Transhepatic Balloon Dilation of Biliary-Enteric Anastomotic Strictures after Surgical Repair of Iatrogenic Bile Duct Injuries

Purpose

To evaluate the efficacy of percutaneous balloon dilation of biliary-enteric anastomotic strictures resulting from surgical repair of laparoscopic cholecystectomy-related bile duct injuries.

Material and Methods

A total of 61 patients were referred to our institution from 1995 to 2010 for treatment of obstruction at the biliary-enteric anastomosis following surgical repair of laparoscopic cholecystectomy-related bile duct injuries. Of these 61 patients, 27 underwent surgical revision upon stricture diagnosis, and 34 patients were managed using balloon dilation. Of these 34 patients, 2 were lost to follow up, leaving 32 patients for analysis. The primary study objective was to determine the clinical success rate of balloon dilation of biliary-enteric anastomotic strictures. Secondary study objectives included determining anastomosis patency, rates of stricture recurrence following treatment, and morbidity.

Results

Balloon dilation of biliary-enteric anastomotic strictures was clinically successful in 21 of 32 patients (66%). Anastomotic stricture recurred in one of 21 patients (5%) after an average of 13.1 years of follow-up. Patients who were unsuccessfully managed with balloon dilation required significantly more invasive procedures (6.8 v. 3.4; p = 0.02) and were left with an indwelling biliary catheter for a significantly longer period of time (8.8 v. 2.0 months; p = 0.02) than patients whose strictures could be resolved by balloon dilation. No significant differences in the number of balloon dilations performed (p = 0.17) or in the maximum balloon diameter used (p = 0.99) were demonstrated for patients with successful or unsuccessful balloon dilation outcomes.

Conclusion

Percutaneous balloon dilation of anastomotic biliary strictures following surgical repair of laparoscopic cholecystectomy-related injuries may result in lasting patency of the biliary-enteric anastomosis.     

新型可降解支架治疗食管吻合口瘘的疗效分析

目的:评价新型生物可降解支架治疗颈部食管吻合口瘘的效果,为治疗食管吻合口瘘提供理论依据。方法:将成年健康新西兰大白兔采用切开吻合置管造瘘法建立颈部食管吻合口瘘的动物模型,1周后,食管造影确定食管瘘口完成。完全随机分组,空白对照组(A组,n=5),对照组(B组,n=5)和实验组(C组,n=5)。实验组使用生物可降解支架封闭瘘口,而对照组应用同规格不可降解支架封堵食管瘘口。植入后每周行食管造影,观察支架及瘘口情况,植入后8周为实验终点。结果:本研究成功建立了兔颈部食管吻合口瘘的动物模型,至实验终点,普通支架组,支架覆盖瘘口,未发生支架移位及穿孔等现象。新型可分解支架组,3例支架分别在支架植入后5-8周分解,发生移位。实验组与对照组闭合率无统计学意义(4/5比3/5,P0.05)。结论:新型生物可降解支架支架是治疗食管吻合口瘘的一种有效方法。     

胸腹腔镜联合食管癌切除术对食管癌患者肺功能、免疫功能的影响及颈部吻合口瘘的影响因素探讨

摘要 目的：探讨胸腹腔镜下进行食管癌切除术对患者肺功能、免疫功能的影响,并分析颈部吻合口瘘的影响因素。方法：选择2016年8月至2021年8月期间我院收治的130例食管癌患者,均成功实施胸腹腔镜联合食管癌切除术,观察手术前后肺功能、免疫功能的变化情况。观察130例患者术后颈部吻合口瘘发生率,采用多因素Logistic回归分析颈部吻合口瘘的影响因素。结果：术后7d,患者的第1s用力呼气量（FEV₁）、用力肺活量（FVC）、呼气流量峰值（PEF）较术前下降（P<0.05）。术后当天、术后7天,患者的CD3⁺、CD4⁺、CD4⁺ /CD8⁺较术前下降后升高,CD8⁺较术前升高后下降（P<0.05）。130例患者术后有28例发生颈部吻合口瘘,发生率为21.54%。均为术后3~18 d内确诊为颈部吻合口瘘,按照是否发生颈部吻合口瘘将患者分为有吻合口瘘组（n=28）和无吻合口瘘组（n=102）。颈部吻合口瘘的发生与术前白蛋白、体质量指数（BMI）、糖尿病史、病变位置、吻合方式、手术时间、术中出血总量、重症呼吸室（ICU）时间、呼吸机使用时间、纤支镜吸痰次数、术后出现肺部感染、住院时间有关（P<0.05）。多因素Logisitic回归分析结果显示：术前白蛋白偏低、病变位置位于上段、术后出现肺部感染、糖尿病史、吻合方式为手工吻合、住院时间偏长是食管癌患者术后发生颈部吻合口瘘的危险因素（P<0.05）。结论：胸腹腔镜联合食管癌切除术治疗食管癌患者,可有效减轻免疫抑制,但不可避免的会影响机体的肺功能,且颈部吻合口瘘的发生受到术前白蛋白、病变位置、术后出现肺部感染等多方面的影响,应着重关注此类患者,以防吻合口瘘的发生。     

恶性胆道梗阻患者所行经皮穿刺肝内胆管引流术中成功置入金属支架的术前影响因素分析

目的:探讨恶性胆道梗阻患者行PTBD(Percutaneous Transhepatic Biliary Drainage)术中金属支架置入成功率的影响因素。方法:回顾性搜集2010年10月-2017年1月上海市第一人民医院收治的因患有近端恶性胆道梗阻行PTBD术患者的相关临床资料。比较不同原发病因患者支架置入情况。根据患者支架置入是否成功将其分为支架组和非支架组,比较患者的一般临床特征。结果:胰腺癌、胃癌和胆囊癌为本研究中数量上前3位的肿瘤,将以上3组分别按照支架置入数行x~2检验,其中胰腺癌(n=18,支架=6)和胃癌(n=14,支架=11)有统计学意义。将50例患者分为支架组(n=28)和非支架组(n=22),组间比较差异有统计学意义的因素包括:白细胞计数(支架组=6.40±3.40×10~9/L,非支架组=10.74±6.41×10~9/L),中性粒细胞计数(支架组=4.90±3.06×10~9/L,非支架组=8.92±6.25×10~9/L),胆道感染(支架组=9,非支架组=15)。进一步将该50例患者分为6组:胰腺癌-胆道感染组、胃癌-胆道感染组、其他肿瘤-胆道感染组、胰腺癌+胆道感染组、胃癌+胆道感染组、其他肿瘤+胆道感染组。将以上6组分别按照支架置入数行x~2检验,胰腺癌+胆道感染组(n=11,支架=1,P=0.001)有统计学意义。结论:PTBD术对于恶性胆道梗阻是一种有效的姑息治疗手段。胆道感染是PTBD术中支架置入成功的不利因素,胰腺癌合并胆道感染会显著降低PTBD术中支架置入成功率。     

磁压榨技术建立大鼠胃肠吻合模型的实验研究

目的:探讨采用磁压榨技术建立大鼠胃肠吻合模型的可行性。方法:设计加工适用于大鼠胃肠吻合的子、母磁体。将10只SD大鼠采用磁压榨技术进行胃肠吻合,子、母磁体分别经口置入大鼠胃和空肠内,子母磁体相吸压榨胃壁和肠壁,磁体间受压组织缺血坏死后连同磁体从吻合口脱落入肠道,胃肠吻合即建立,磁体最终经消化道自行排出体外,术后2周处死动物,获取吻合口标本,检测吻合口爆破压、肉眼和光镜下观察吻合口愈合情况。结果:10只SD大鼠中,1只因麻醉意外死亡,其余9只大鼠均顺利完成手术操作并存活至术后2周;手术平均操作时间(15.89±3.25)min,磁体排出体外时间(8.56±1.26)天(范围7-11)天;吻合口爆破压均大于200 mm Hg,吻合口组织HE染色和Masson染色可见粘膜层连续性建立,愈合良好。结论:磁压榨技术可用于大鼠胃肠吻合模型制备,具有操作简单、成功率高的优点。     

A simple method for sutureless gastrointestinal anastomosis in rat.

A simple tubing stent was attempted to test a model for sutureless gastrointestinal anastomosis in 6 male rats at the age of 15 weeks. In the 3rd and 4th weeks after the operation, X-ray examination demonstrated that the gastrointestinal passage in the anastomotic site was quite satisfactory. There was no incidence of anastomotic leakage. In the 6th week after the operation, there were no macroscopic or microscopic ruptures, nor were there any obstructions at the anastomotic site. This simple sutureless method was effective at preparing anastomosis in the gastrointestinal tract in the rat and could be applied to other small experimental animals.     

胆道支架置入联合介入化疗对恶性胆道梗阻患者肝功能及预后的影响

目的:研究胆道支架置入联合介入化疗对恶性胆道梗阻患者肝功能及预后的影响,为临床治疗提供依据。方法:选取2013年2月到2015年2月我院收治的恶性胆道梗阻患者90例,按照随机数字表法将患者分为Ⅰ组、Ⅱ组和Ⅲ组,每组30例,Ⅰ组给予胆道支架置入联合介入化疗,Ⅱ组给予单纯胆道支架置入,Ⅲ组给予保守治疗,比较三组治疗前、后肝功能、并发症、支架通畅率及生存期。结果:治疗前三组谷草转氨酶(AST)、谷丙转氨酶(ALT)、γ-谷氨酰转移酶(r-GT)比较无统计学意义(P0.05),治疗后Ⅰ组和Ⅱ组AST、ALT和r-GT均显著改善,与治疗前和Ⅲ组比较差异具有统计学意义(P0.05),且I组显著优于Ⅱ组,比较差异具有统计学意义(P0.05),Ⅲ组治疗后AST、ALT和r-GT与治疗前比较差异无统计学意义(P0.05);Ⅰ组、Ⅱ组和Ⅲ组并发症发生率比较无统计学意义(P0.05);Ⅰ组术后3个月、6个月和12个月支架通畅率均显著高于Ⅱ组,比较差异具有统计学意义(P0.05);I组生存期显著高于Ⅱ组和Ⅲ组,Ⅱ组高于Ⅲ组,比较差异具有统计学意义(P0.05)。结论:胆道支架置入联合介入化疗治疗恶性胆道梗阻具有较好效果,能明显改善患者肝功,延长患者生存期。     

Comparative analysis of human UCB and adipose tissue derived mesenchymal stem cells for their differentiation potential into brown and white adipocytes

The differentiation potential of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) into brown and white adipocytes in comparison to Adipose tissue derived MSCs (AD-MSCs) were investigated in order to characterize their potency for future cell therapies. MSCs were isolated from ten UCB samples and six liposuction materials. MSCs were differentiated into white and brown adipocytes after characterization by flow cytometry. Differentiated adipocytes were stained with Oil Red O and hematoxylin/eosin. The UCP1 protein levels in brown adipocytes were investigated by immunofluoresence and western blot analysis. Cells that expressed mesenchymal stem cells markers (CD34?, CD45?, CD90+ and CD105+) were successfully isolated from UCB and adipose tissue. Oil Red O staining demonstrated that white and brown adipocytes obtained from AD-MSCs showed 85 and 61% of red pixels, while it was 3 and 1.9%, respectively for white and brown adipocytes obtained from UCB-MSCs. Fluorescence microscopy analysis showed strong uncoupling protein 1 (UCP1) signaling in brown adipocytes, especially which were obtained from AD-MSCs. Quantification of UCP1 protein amount showed 4- and 10.64-fold increase in UCP1 contents of brown adipocytes derived from UCB-MSCs and AD-MSCs, respectively in comparison to undifferentiated MSCs (P?<?0.004). UCB-MSCs showed only a little differentiation tendency into adipocytes means it is not an appropriate stem cell type to be differentiated into these cell types. In contrast, high differentiation efficiency of AD-MSCs into brown and white adipocytes make it appropriate stem cell type to use in future regenerative medicine of soft tissue disorders or fighting with obesity and its related disorders.     

Precise Reconstruction of Veins and Bile Ducts in Rat Liver Transplantation

Rat orthotopic liver transplantation (ROLT) remains a technically demanding procedure, especially regarding the reconstruction of the suprahepatic vena cava (SHVC). In this study, a new microsuture technique was developed for anastomosis of the SHVC, and a special single-groove cuff and blade-cut stent were introduced. With these modified techniques, we aimed to make a precise anastomosis of the SHVC and to provide optimal cuffs and stents for the reconstruction of the veins and bile ducts. According to different microsuture techniques for the SHVC and different types of cuffs and stents, three ROLT groups were created to compare the operation times and prognoses. Sham operations were performed as controls in the fourth group. The time expenditures with each step were compared among the transplantation groups. Biochemical parameters were tested at the end of a 1-month observation period. The short- and long-term survival rates of the transplantation groups were recorded and compared. Our new microsuture technique was faster than the conventional continuous suture technique for SHVC anastomosis (P < 0.05). The use of a single-groove cuff for reconstruction of the portal vein and the infrahepatic vena cava shortened the anastomotic time (P < 0.05). The use of blade-cut stents resulted in fewer biliary complications and better survival over the short and long terms (P < 0.05). Our new microsuture technique and the single-groove cuffs proved to be a precise method for venous reconstruction which shortened the anhepatic time and the anastomotic time significantly. The blade-cut stents apparently reduced the incidence of biliary complications. In summary, with this precise microsuture technique and delicate cuffs and stents, excellent long-term survival can be achieved easily and stably for ROLT.     

Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis

Background aimsAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of brain and spinal cord motor neurons (MN). The intraspinal and systemic grafting of mesenchymal stromal cells (MSC) was used to treat symptomatic transgenic rats overexpressing human superoxide dismutase 1 (SOD1) in order to alleviate the disease course and prolong the animals’ lifespan.MethodsAt the age of 16 weeks (disease onset) the rats received two grafts of MSC expressing green fluorescent protein (GFP⁺ MSC) on the same day, intraspinally (10⁵ cells) and intravenously (2 × 10⁶ cells). Sham-treated animals were injected with phosphate-buffered saline (PBS). Motor activity, grip strength and body weight were tested, followed by immunohistochemical analysis.ResultsThe combined grafting of MSC into symptomatic rats had a significant effect on motor activity and grip strength starting 4 weeks after transplantation. The lifespan of animals in the treated group was 190 ± 3.33 days compared with 179 ± 3.6 days in the control group of animals. Treated rats had a larger number of MN at the thoracic and lumbar levels; these MN were of larger size, and the intensity of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining in the somas of apoptotic MN at the thoracic level was much lower than in sham-treated animals. Transplanted GFP⁺ MSC survived in the spinal cord until the end stage of the disease and migrated both rostrally and caudally from the injection site.ConclusionsIntraspinal and intravenous transplantation of MSC has a beneficial and possibly synergistic effect on the lifespan of ALS animals.     

RECONSTRUCTIVE OPERATIONS ON THE BILIARY TRACT

Fifty cases in which reconstruction of the biliary system was carried out were reviewed. In 25 cases the operation was done during the treatment of malignant neoplasms. The other 25 patients were treated for benign conditions. Delayed stricture of the biliary anastomosis occurs more frequently following operation for benign post-traumatic obstruction than following reconstruction for other conditions. This is probably a result of: (1) greater regional scarring, (2) local infection, and (3) technical imperfections in the reconstituted biliary anastomosis.Certain primary malignant tumors may be difficult to recognize by both gross and microscopic examination. In six cases of biliary obstruction resulting from malignant neoplasms in the present series, exploration had been carried out some time previously, and in four of them an erroneous diagnosis of benign biliary obstruction was made.End-to-end anastomosis of the duct above and below the point of obstruction is the method preferred in the treatment of benign biliary stricture. Intrahepatic and extrahepatic biliary-enteric anastomoses have been used successfully in selected cases.     

Non-enzymatic dissociation of human mesenchymal stromal cells improves chemokine-dependent migration and maintains immunosuppressive function

Background aimsHuman bone marrow–derived mesenchymal stromal cells (MSC) can suppress inflammation; therefore their therapeutic potential is being explored in clinical trials. Poor engraftment of infused MSC limits their therapeutic utility; this may be caused by MSC processing before infusion, in particular the method of their detachment from culture.MethodsEnzymatic methods of detaching MSC (Accutase and TrypLE) were compared with non-enzymatic methods (Cell Dissociation Buffer [CDB], ethylenediamine tetra-acetic acid and scraping) for their effect on MSC viability, chemokine receptor expression, multi-potency, immunomodulation and chemokine-dependent migration.ResultsTrypLE detachment preserved MSC viability and tri-lineage potential compared with non-enzymatic methods; however, this resulted in near complete loss of surface chemokine receptor expression. Of the non-enzymatic methods, CDB detachment preserved the highest viability while retaining significant tri-lineage differentiation potential. Once re-plated, CDB-detached MSC regained their original morphology and reached confluence, unlike with the use of other non-enzymatic methods. Viability was significantly reduced with the use of ethylenediamine tetra-acetic acid and further reduced with the use of cell scraping. Addition of 1% serum during CDB detachment led to higher MSC numbers entering autophagy and increased MSC recovery after re-plating. TrypLE and CDB-detached MSC suppressed CD3⁺CD4⁺CD25⁻ T-cell proliferation, although TrypLE-detached MSC exhibited superior suppression at 1:20 ratio. CDB detachment retained surface chemokine receptor expression and consequently increased migration to CCL22, CXCL12 and CCL4, in contrast with TrypLE-detached MSC.ConclusionsThis study demonstrates that non-enzymatic detachment of MSC with the use of CDB minimizes the negative impact on cell viability, multipotency and immunomodulation while retaining chemokine-dependent migration, which may be of importance in MSC delivery and engraftment in sites of injury.     

Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.     

Effect of a honey and arginine-glutamine-hydroxymethylbutyrate mixture on the healing of colon anastomosis in rats immunosuppressed with tacrolimus

ABSTRACT

We compared the effect of honey and a mixture of arginine-glutamine-hydroxymethylbutyrate (AGHMB) on healing of a descending colon anastomosis in rats that were immunosuppressed with tacrolimus (Tac). Sprague-Dawley rats were divided into four groups: untreated control, Tac, Tac + honey and Tac + AGHMB. Colon resection and anastomosis were performed on day 14 and re-laparotomy was performed on the day 21 of the study. Anastomotic bursting pressure, macroscopic adhesion score, weekly body weight changes, histopathological features and immunohistochemical staining of TGF-β1 were determined for all groups. We found no significant difference in anastomotic bursting pressure among the experimental groups. We found significant weekly increases in body weight for the Tac + honey group. We found no significant difference in the weekly body weight measurements for the Tac + AGHMB group. We found significant increases in TGF-β1 expression in the Tac + honey group compared to the control and Tac groups. No significant differences in inflammatory cell infiltration, fibroblast proliferation or collagen deposition were found between the Tac + honey and Tac + AGHMB groups; however, a significant difference in neovascularization between these groups was found. Neovascularization in the Tac + honey group was significantly greater than for the Tac + AGHMB group. We found that both honey and the AGHMB mixture were beneficial for anastomotic wound healing in rats that were immunosuppressed using Tac.     

Human bone marrow mesenchymal cells express NG2: possible increase in discriminative ability of flow cytometry during mesenchymal stromal cell identification

Background aimsMesenchymal stromal cells (MSC) exhibit non-specific hematopoietic cell and/or stromal cell markers (e.g. CD73, CD105 and CD166) that have been used to identify MSC by flow cytometry. Because a neural glial antigen, NG2 (a progenitor cell marker in the central nervous system), is expressed by several tissue cells originating in the mesenchyme but not hematopoietic cells, it might be useful for isolating and identifying MSC. We investigated NG2 expression on culture-expanded MSC by flow cytometry.MethodsHuman bone marrow (BM) samples taken from 12 donors were cultured for MSC to be used in up to nine serial passages. Using flow cytometry, the neural glial antigen NG2 and commonly used MSC markers CD73, CD105 and CD166, were analyzed on the surface of culture-expanded MSC. The multipotential differentiation of the MSC was examined by adipogenic and osteogenic induction.ResultsThe percentage of cells positive for NG2 was similar to the percentages of cells positive for CD73, CD105 and CD166 in all passages of BM samples. The mean fluorescent intensities of NG2 did not change with culture passage. The MSC was successfully differentiated into adipogenic and osteogenic lines. The cells showed no karyotypic abnormalities.ConclusionsNG2 seems to be a promising marker for investigating the biology of MSC.     

内镜下萨氏扩张器扩张联合局部注射曲安奈德治疗食管良性吻合口狭窄的疗效及安全性研究

目的:探讨食管良性吻合口狭窄经内镜下萨氏扩张器扩张联合局部注射曲安奈德治疗的临床疗效及安全性。方法:选取79例食管良性吻合口狭窄患者作为研究对象,根据数字表法将其随机分为对照组(n=38)和研究组(n=41),对照组给予内镜下萨氏扩张器扩张治疗,研究组在对照组基础上联合局部注射曲安奈德治疗,比较两组患者临床疗效、术后恢复情况以及安全性。结果:研究组治疗后总有效率为85.37%(35/41),高于对照组患者的65.79%(25/38)(x~2=4.138,P=0.002)。研究组持续症状缓解时间、再次进行内镜下扩张治疗的间隔时间均长于对照组(t=21.573、27.209,P=0.000、0.000),两组患者治疗前Stooler评分比较差异无统计学意义(t=0.266,P=0.791),两组患者治疗后Stooler评分均降低(t=16.606、25.962,P=0.000、0.000),且研究组低于对照组(t=7.407,P=0.000)。研究组术后并发症总发生率为19.51%(8/41),低于对照组患者的42.11%(16/38)(x~2=4.760,P=0.009)。结论:食管良性吻合口狭窄经内镜下萨氏扩张器扩张联合局部注射曲安奈德治疗后,可获得较好的疗效,患者临床症状得到改善,同时还可减少并发症发生率,临床应用价值较高。     

Mesenchymal stem cells as a gene therapy carrier for treatment of fibrosarcoma

Background aimsCell-based gene therapy is an alternative to viral and non-viral gene therapy. Emerging evidence suggests that mesenchymal stem cells (MSC) are able to migrate to sites of tissue injury and have immunosuppressive properties that may be useful in targeted gene therapy for sustained specific tissue engraftment.MethodsIn this study, we injected intravenously (i.v.) 1 × 10⁶ MSC, isolated from green fluorescent protein (GFP) transgenic rats, into Rif-1 fibrosarcoma-bearing C3H/HeN mice. The MSC had been infected using a lentiviral vector to express stably the luciferase reporter gene (MSC-GFP-luci). An in vivo imaging system (IVIS 200) and Western blotting techniques were used to detect the distribution of MSC-GFP-luci in tumor-bearing animals.ResultsWe observed that xenogenic MSC selectively migrated to the tumor site, proliferated and expressed the exogenous gene in subcutaneous fibrosarcoma transplants. No MSC distribution was detected in other organs, such as the liver, spleen, colon and kidney. We further showed that the FGF2/FGFR pathways may play a role in the directional movement of MSC to the Rif-1 fibrosarcoma. We performed in vitro co-culture and in vivo tumor growth analysis, showing that MSC did not affect the proliferation of Rif-1 cells and fibrosarcoma growth compared with an untreated control group. Finally, we demonstrated that the xenogenic MSC stably expressing inducible nitric oxide synthase (iNOS) protein transferred by a lentivirus-based system had a significant inhibitory effect on the growth of Rif-1 tumors compared with MSC alone and the non-treatment control group.ConclusionsiNOS delivered by genetically modified iNOS-MSC showed a significant anti-tumor effect both in vitro and in vivo. MSC may be used as a target gene delivery vehicle for the treatment of fibrosarcoma and other tumors.     

Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis

Mesenchymal stem cells (MSCs) hold promise for cell-based therapy in regenerative medicine. To date, MSCs have been obtained from conventional bone marrow via a highly invasive procedure. Therefore, MSCs are now also isolated from sources such as adipose tissue, cord blood and cord stroma, a subject of growing interest. As the characterization and differentiation potential of adipose-derived MSCs (AD-MSCs) and bone-marrow-derived MSCs (BM-MSCs) have not been documented, we have evaluated and compared the characteristics of both MSC types by qualitative and quantitative analyses. Both cell types show similar morphology and surface protein expression, being positive for stromal-associated markers and negative for hematopoietic and endothelial markers. The colony-forming potential of AD-MSCs is distinctly higher than that of BM-MSCs. Nonetheless, similar adipogenic and osteogenic differentiation is observed in both groups of MSCs. Cytochemical qualitative analysis and calcium mineralization demonstrate higher levels toward osteogenic differentiation in BM-MSCs than in AD-MSCs. On the contrary, the percentage of Nile red oil staining for differentiated adipocytes is higher in AD-MSCs than in BM-MSCs. Quantitative real-time polymerase chain reaction shows similar patterns of osteogenic- and adipogenic-associated gene expression in both cell types. Each of the MSCs respond in functional analysis by exhibiting unique properties at the differentiation level according to their micro-environmental niche. Thus, quantitative analysis might be a valuable means of describing stem cell multipotency, in addition to qualitative investigation.