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Hu Y.-L.,Zhejiang University | Miao P.-H.,Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces | Huang B.,Zhejiang University | Zhang T.-Y.,Zhejiang University | And 3 more authors.
Journal of Biomedical Nanotechnology | Year: 2014

Mesenchymal stem cells (MSCs) are a promising tool for delivering of therapeutic agents in cancer treatment. In the present study, our findings suggested that both i.v. and intratumoral injection of MSCs could favor tumor growth under physiologic conditions. However, the anti-tumor effects of MSC-IL-12 were achieved using our strategy. Unlike the previously reported method, the genetic engineering of MSCs was conducted by non-viral transfection using the new vector, spermine-pullulan. The transfection, cytotoxicity, and the cellular internalization of this vector were evaluated. Then, the therapeutical gene, IL-12, was delivered to the MSCs using this vector. The in vitro secretions of IL-12 by MSC-IL-12 confirmed the success of using spermine-pullulan/DNA nanoparticles for the gene transfection. We used the MSC-IL-12 for the in vivo treatment of both B16F10 metastasis tumor and the established subcutaneous B16BL6 tumor. For the B16F10 metastasis tumor, treatment with MSC-IL-12 significantly reduced lung metastases. For the established subcutaneous B16BL6 tumor, intratumoral injected MSC-IL-12 cells considerably retarded tumor growth. Prolonged survival was observed when MSC-IL-12 cells were injected through the tail vein or intratumorally, indicating that the MSCs engineered with the therapeutic gene could reverse the tumor-promoting effects of MSCs using the nonviral transduction method. However, the intravenous injected MSC-IL-12 did not prevent the tumor growth of the established subcutaneous B16BL6 tumor. Thus, we examined the the in vivo distribution of MSCs in different organs and it was found that MSCs were mainly distributed in the lungs, which may explain the inability of intravenously injected MSC-IL-12 to inhibit the growth of the established subcutaneous tumor. Copyright © 2014 American Scientific Publishers All rights reserved.


Hu Y.-L.,Zhejiang University | Huang B.,Zhejiang University | Zhang T.-Y.,Zhejiang University | Miao P.-H.,Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces | And 3 more authors.
Molecular Pharmaceutics | Year: 2012

The success of gene therapy relies largely on an effective targeted gene delivery system. Till recently, more and more targeted delivery carriers, such as liposome, nanoparticles, microbubbles, etc., have been developed. However, the clinical applications of these systems were limited for their several disadvantages. Therefore, design and development of novel drug/gene delivery vehicles became a hot topic. Cell-based delivery systems are emerging as an alternative for the targeted delivery system as we described previously. Mesenchymal stem cells (MSCs) are an attractive cell therapy carrier for the delivery of therapeutic agents into tumor sites mainly for their tumor-targeting capacities. In the present study, a nonviral vector, PEI600-Cyd, prepared by linking low molecular weight polyethylenimine (PEI) and β-cyclodextrin (β-CD), was used to introduce the therapeutical gene, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), to MSCs. Meanwhile, the characterization, transfection efficiency, cytotoxicity, cellular internalization, and its mechanism of this nonviral vector were evaluated. The in vitro expression of TRAIL from MSCs-TRAIL was demonstrated by both enzyme-linked immunosorbent assay and Western blot analysis. The lung tumor homing ability of MSCs was further confirmed by the in vitro and in vivo model. Moreover, the therapeutic effects as well as the safety of MSCs-TRAIL on lung metastases bearing C57BL/6 mice and normal C57BL/6 mice were also demonstrated. Our results supported both the effectiveness of nonviral vectors in transferring the therapeutic gene to MSCs and the feasibility of using MSCs as a targeted gene delivery carrier, indicating that MSCs could be a promising tumor target delivery vehicle in cancer gene therapy based on nonviral gene recombination. © 2012 American Chemical Society.


Miao P.-H.,Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces | Hu Y.-L.,Zhejiang University | Huang B.,Zhejiang University | Gao J.-Q.,Zhejiang University | And 2 more authors.
Materials Express | Year: 2013

The current study aimed to examine the transfection ability of chitosan-linked-polyethylenimine (PEI) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). Firstly, series of CP/DNA complex with different charge ratio (N/P) were prepared, and the physiochemical properties, such as particle size and the zeta potential of this vector, were measured. Analysis of its physicochemical properties demonstrated that the modified PEI polymers were able to form nanoparticles with DNA whose particle size ranging from 110-140 nm. And their surface charge decreased to about 24 mV. Then, the in vitro cellular internalization was observed under a confocal laser scanning microscope, followed by the transfection efficiency examination in mesenchymal stem cells (MSCs). Also, its cytotoxicity was compared with that of PEI by MTT assay. It was found that the novel CP polymer exhibited higher transfection efficiency and relatively lower cytotoxicity in MSCs than the control. Finally, the transfection of TGF-β1 based on CP was proved to successfully induce the osteogenic differentiation of MSCs in vitro. In conclusion, that the newly synthesized CP can form a complex with DNA, and had compatible physicochemical properties for use as a gene delivery system. Our result demonstrated that the CP would be a very attractive non-viral vector which can be utilized in MSCs. © 2013 by American Scientific Publishers All rights reserved.


Mo G.S.,Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2011

To evaluate the efficacy and potential renal impairment of one-year combination therapy de novo of adefovir dipivoxil (ADV) and lamivudine (LMV) for decompensated cirrhosis related to HBV. A total of 36 patients with decompensated cirrhosis related to HBV, nobody had nucleos(t)ide analogs (NAs) treatment history, were recruited and were divided into two group (control group and observation group) randomly. A monotherapy of LMV (100 mg per day) was selected to individuals in control group (n = 18), in contrast, a combination therapy de novo of ADV (10 mg per day) and LMV (100 mg per day) was applied to those in observation group (n = 18). Basic approaches including liver protection, symptom-driven intervention, and supporting therapy, were given to all of the individuals. A course of one year was applied to all. Liver function, Child-Pugh score, serum creatinine (sCr) level, virological response (VR) rate, and virological breakthrough rate were observed pro- and post- treatment, differences between the two populations were analysed statistically. (1) The averages of gender, age, HBeAg status, HBV viral load, sCr level, and Child-Pugh score were all compatible in the two groups at baseline (P > 0.05 for all). (2) At the endpoint of treatment, none of deaths was reported. Comparing with the status before treatment in each group itself, liver function, Child-Pugh score, and viral load were improved statistically (P < 0.01 for all), especially in observed group (P < 0.01 for all variables, vs control group), as for VR rate, result is significant superior to that of control group too (88.89% vs 66.67% , P < 0.05). (3) Virological breakthrough occurred to none in observed group and three cases (16.67%) in control group, all of them were confirmed to be rtM204V variant in the following detection of direct sequencing. (4) Elevated level of sCr didn't arised at the end of treatment in two groups. Present study reveals that in populations with decompensated cirrhosis related to HBV, one-year combination therapy de novo of ADV and LMV is superior to monotherapy of LMV, and the renal safety is favorable within one year.


Cui Y.,Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

To evaluate the results of thumb opposition function by transferring the extensor carpi ulnaris and the extensor pollicis brevis muscle tendons. Between March 2006 and August 2009, 35 patients with dysfunction of thumb opposition were treated and the thumb opposition function was reconstructed by transferring the extensor carpi ulnaris and the extensor pollicis brevis muscle tendons. There were 25 males and 10 females with an average age of 33.5 years (range, 20-53 years); 20 had median nerve injury in the wrist and 15 had median nerve injury with ulnar nerve injury. The causes were sharp instrument injury in 24 cases, blunt injury in 9 cases, and hot crush injury in 2 cases. Six cases complicated by shaft fractures of radius and ulna. All the patients underwent an operation of nerve repair at 1 to 3 hours after injury (mean, 2 hours). The time from injury to reconstructing operation was 6-14 months (mean, 7.5 months). Two cases was able to abduct thumb slightly, the others had no functions of thumb abduct and thumb opposition. All the wounds gained the primary healing. The patients were followed up 12-18 months (mean, 14 months). The wrist joint angle and thumb dorsal extension were satisfactory. Thumb abduct and thumb opposition function returned to normal in 20 patients with simple median nerve injury; in 15 patients with median nerve injury and ulnar nerve injury, thumb abduct and thumb opposition function returned to normal in 15 and 13, respectively. According to ZHAO Shuqiang's standard, the results of thumb opposition function were normal in all patients at 12 months after operation. It is a convenient and efficient procedure to reconstruct thumb opposition function by transferring the extensor carpi ulnaris and the extensor pollicis brevis muscle tendons.


Pan Y.,Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2011

To evaluate the effectiveness of vacuum sealing drainage (VSD) combined with skin grafting to repair donor site for wrap around flap of hallux toe. From Jan. 2009 to Apr. 2010,20 patients with injury of hallux toe were repaired by wrap around flap of hallux. There were 16 males and 4 females,with ranging in age from 18 to 45 years (averaged 36 years). The causes of injury: mechanical injury in 18 cases, road accident in 1 and postoperative hemangioma of hallux in 1. The degree of hallux defect as follow: grade I 10 cases, grade II 6 cases, grade III 4 cases. All patients' feet underwent 64-row CT angiography pre-operation, there were exposed bone and tendon tissue, the area of hallux ranged from 5 cm x 3 cm to 7 cm x 5 cm, all cases underwent vacuum sealing drainage combined with dermatoplasty of full thick skin graft for repair of donor site for wrap around flap of hallux toe. The raw surface of donor site in all patients survived without complications such as skin ulceration and exudation. After follow-up for 3 to 12 months, the skin appearance of raw surface was excellent with well function. VSD associated with dermatoplasty of full thick skin graft to repair donor site for wrap around flap of hallux toe can obtain satisfactory effect in treating injury of hallux toe, which can reduce difficulty of wound healing, improve skin appearance of donor site and relieve pain of patients.


PubMed | Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Type: Journal Article | Journal: Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2011

To evaluate the effectiveness of vacuum sealing drainage (VSD) combined with skin grafting to repair donor site for wrap around flap of hallux toe.From Jan. 2009 to Apr. 2010,20 patients with injury of hallux toe were repaired by wrap around flap of hallux. There were 16 males and 4 females,with ranging in age from 18 to 45 years (averaged 36 years). The causes of injury: mechanical injury in 18 cases, road accident in 1 and postoperative hemangioma of hallux in 1. The degree of hallux defect as follow: grade I 10 cases, grade II 6 cases, grade III 4 cases. All patients feet underwent 64-row CT angiography pre-operation, there were exposed bone and tendon tissue, the area of hallux ranged from 5 cm x 3 cm to 7 cm x 5 cm, all cases underwent vacuum sealing drainage combined with dermatoplasty of full thick skin graft for repair of donor site for wrap around flap of hallux toe.The raw surface of donor site in all patients survived without complications such as skin ulceration and exudation. After follow-up for 3 to 12 months, the skin appearance of raw surface was excellent with well function.VSD associated with dermatoplasty of full thick skin graft to repair donor site for wrap around flap of hallux toe can obtain satisfactory effect in treating injury of hallux toe, which can reduce difficulty of wound healing, improve skin appearance of donor site and relieve pain of patients.


PubMed | Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Type: Journal Article | Journal: Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2011

To evaluate the efficacy and potential renal impairment of one-year combination therapy de novo of adefovir dipivoxil (ADV) and lamivudine (LMV) for decompensated cirrhosis related to HBV.A total of 36 patients with decompensated cirrhosis related to HBV, nobody had nucleos(t)ide analogs (NAs) treatment history, were recruited and were divided into two group (control group and observation group) randomly. A monotherapy of LMV (100 mg per day) was selected to individuals in control group (n = 18), in contrast, a combination therapy de novo of ADV (10 mg per day) and LMV (100 mg per day) was applied to those in observation group (n = 18). Basic approaches including liver protection, symptom-driven intervention, and supporting therapy, were given to all of the individuals. A course of one year was applied to all. Liver function, Child-Pugh score, serum creatinine (sCr) level, virological response (VR) rate, and virological breakthrough rate were observed pro- and post- treatment, differences between the two populations were analysed statistically.(1) The averages of gender, age, HBeAg status, HBV viral load, sCr level, and Child-Pugh score were all compatible in the two groups at baseline (P > 0.05 for all). (2) At the endpoint of treatment, none of deaths was reported. Comparing with the status before treatment in each group itself, liver function, Child-Pugh score, and viral load were improved statistically (P < 0.01 for all), especially in observed group (P < 0.01 for all variables, vs control group), as for VR rate, result is significant superior to that of control group too (88.89% vs 66.67% , P < 0.05). (3) Virological breakthrough occurred to none in observed group and three cases (16.67%) in control group, all of them were confirmed to be rtM204V variant in the following detection of direct sequencing. (4) Elevated level of sCr didnt arised at the end of treatment in two groups.Present study reveals that in populations with decompensated cirrhosis related to HBV, one-year combination therapy de novo of ADV and LMV is superior to monotherapy of LMV, and the renal safety is favorable within one year.


PubMed | Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Type: Journal Article | Journal: Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

To evaluate the results of thumb opposition function by transferring the extensor carpi ulnaris and the extensor pollicis brevis muscle tendons.Between March 2006 and August 2009, 35 patients with dysfunction of thumb opposition were treated and the thumb opposition function was reconstructed by transferring the extensor carpi ulnaris and the extensor pollicis brevis muscle tendons. There were 25 males and 10 females with an average age of 33.5 years (range, 20-53 years); 20 had median nerve injury in the wrist and 15 had median nerve injury with ulnar nerve injury. The causes were sharp instrument injury in 24 cases, blunt injury in 9 cases, and hot crush injury in 2 cases. Six cases complicated by shaft fractures of radius and ulna. All the patients underwent an operation of nerve repair at 1 to 3 hours after injury (mean, 2 hours). The time from injury to reconstructing operation was 6-14 months (mean, 7.5 months). Two cases was able to abduct thumb slightly, the others had no functions of thumb abduct and thumb opposition.All the wounds gained the primary healing. The patients were followed up 12-18 months (mean, 14 months). The wrist joint angle and thumb dorsal extension were satisfactory. Thumb abduct and thumb opposition function returned to normal in 20 patients with simple median nerve injury; in 15 patients with median nerve injury and ulnar nerve injury, thumb abduct and thumb opposition function returned to normal in 15 and 13, respectively. According to ZHAO Shuqiangs standard, the results of thumb opposition function were normal in all patients at 12 months after operation.It is a convenient and efficient procedure to reconstruct thumb opposition function by transferring the extensor carpi ulnaris and the extensor pollicis brevis muscle tendons.


PubMed | Zhejiang Provincial Corps Hospital of Chinese Peoples Armed Police Forces
Type: Journal Article | Journal: Die Pharmazie | Year: 2012

Current efforts had been made to undertake a three-dimensional (3-D) reverse transfection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in PLGA scaffolds. As a kind of multipotent stem cells, BM-MSCs show great potential and tremendous capacity in the gene transfection field and PLGA 3-D scaffold has been shown to be a biomaterial that provides structural support to cells proliferation and tissue engineering. The objective of this study was to assess the transfection efficiency of BM-MSCs with a 3-D reverse transfection method by using PLGA scaffold and observe the SEM photographs of BM-MSCs cultured on PLGA scaffold. BM-MSCs were cultured in 3-D PLGA scaffold which was incorporated with pullulan-spermine/pGL3. It was shown that the gene expression duration of BM-MSCs transfected using 3D reverse method with pullulan-spermine/DNA in the presence of serum maintained 12 days at high levels as compared with the plasmid DNA in medium, and scanning electronic microscopy (SEM) photographs of BM-MSCs cultured on PLGA scaffold exhibited robust cell attachment and viability when cultured in PLGA scaffold in vitro. This study demonstrates that the 3-D reverse transfection method of BM-MSCs using PLGA scaffold could achieve long gene expression in a relatively high level, therefore this transfection system is promising in gene transfection and tissue engineering.

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