Effects of adenovirus hepatocyte growth factor modified bone marrow mesenchymal stem cells on radioactive skin wound healing

doi:10.3969/j.issn.2095-4344.2012.49.019

Abstract

Abstract:

BACKGROUND: Combined application of gene therapy and stem cells can promote the healing of refractory large scale wound.
OBJECTIVE: To observe the effect of adenovirus hepatocyte growth factor (Ad-HGF) modified bone marrow mesenchymal stem cells (BMSCs) on radioactive skin wound healing.
METHODS: The BMSCs were in vitro isolated and cultured from male Wistar rats and transfected with Ad-HGF. Forty female Wistar rats were irradiated using X-ray therapy machine to establish acute skin radiation damage model. The models were randomly divided into four groups: BMSCs treatment group, Ad-HGF treatment group, Ad-HGF modified BMSCs treatment group and control group. After irradiating, the suspension of BMSCs, Ad-HGF and Ad-HGF modified BMSCs suspension were injected directly into the radioactive wounds.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining results showed that at 21 hours after injury, the epidermis in Ad-HGF modified BMSCs treatment group was significantly thinner than that in the control group, and the epidermis in the Ad-HGF modified BMSCs treatment group was more regular than that in the BMSCs treatment group and Ad-HGF treatment group, many small vessels were observed in the derma of radioactive wounds. Immunohistochemistry results showed that the expression of hepatocyte growth factor in Ad-HGF modified BMSCs treatment group was stronger than that in the other three groups; the content of hydroxyproline in the Ad-HGF modified BMSCs treatment group was significantly lower than that in the other three groups after 7 days (P < 0.05); in situ hybridization showed that the expression of sex-determining sry gene in Ad-HGF modified BMSCs treatment group was stronger than that in the BMSCs treatment group. It demonstrates that Ad-HGF modified BMSCs can promote the healing of radioactive skin wound, and the effect is better than simple application of the suspension.

CLC Number:

R394.2

Ha Xiao-qin, Zhang Jun, Deng Zhi-yun, Dong Ju-zi, Peng Jun-hua, Zhao Yong, Zhang Yuan-yuan. Effects of adenovirus hepatocyte growth factor modified bone marrow mesenchymal stem cells on radioactive skin wound healing[J]. Chinese Journal of Tissue Engineering Research, 2012, 16(49): 9226-9231.

Figures/Tables 4

References

[1] Fu XB.Zhongguo Gongchen Kexue.2009;11(10):122-128.付小兵. 组织再生:梦想、希望和挑战[J]. 中国工程科学,2009; 11(10):122-128.

[2] Shen J,Tsai YT,Dimarco NM,et al.Transplantation of mesenchymal stem cells from young donors delays aging in mice.Sci Rep.2011;1:67.

[3] Mariani E,Facchini A.Clinical Applications and biosafety of human adult mesenchymal stem cells.Curr Pharm Des. 2012;1:19.

[4] Mazo M,Arana M,Pelacho B,et al. Mesenchymal stem cells and cardiovascular disease: a bench to bedside roadmap. Stem Cells Int. 2012;2012:175979

[5] Bernardo ME, Locatelli F, Fibbe WE, et al. Mesenchymal stromal cells.Ann N Y Acad Sci.2009;1176(9):101-117.

[6] Dou YR,Fu XB.Zhongguo Weizhongbing Jijiu Yixue. 2004; 16(8):499-501.都义日,付小兵.骨髓间充质干细胞的研究进展[J].中国危重病急救医学,2004,16(8):499-501.

[7] Cao Q,Wang F,Lin J,et al. Mesenchymal stem cells enhance the differentiation of c-kit+ cardiac stem cells. Front Biosc. 2012;17:1323-1328.

[8] Undale AH, Westendorf JJ, Yaszemski MJ, et al. Mesenchymal stem cells for bone repair and metabolic bone diseases.Mayo Clin Proc.2009;84(10):893-902.

[9] Ha XQ, Yuan B,Li YM,et al.Gene Therapy for pathological scar with hepatocyte growth factor mediated by recombinant adenovirus vector.Science in China.2003;46(3):320-327.

[10] Ha XQ, Dong F,Lv TD.Zhongguo Xiufu Chongjian Waike Zazhi. 2010;24(5):613-617.哈小琴,董芳,吕同德.肝细胞生长因子基因对BMSCs的修饰及活性观察[J].中国修复重建外科杂志,2010;24(5):613-617.

[11] Jin LJ,Ha XQ,Zhang C,et al.Xibei Guofang Yixue Zazhi. 2007; 28(1):12-15.金丽娟,哈小琴,张诚,等.Ad-HGF修饰MSCs异体移植对烧伤创面愈合的作用[J].西北国防医学杂志,2007;28(1):12-15

[12] Woessner J. The determination of hydroxyproline in tissue and protein sample contain small proportion of this amino acid. Arch Biochem Biophys.1961;93:440.

[13] Sadiq AA,Geynisman DM,Salgia R. Inhibition of MET receptor tyrosine kinase and its ligand hepatocyte growth factor.J Thorac Oncol. 2011;6(11 Suppl 4):S1810-1.

[14] Nakamura T,Sakai K,Nakamura T,et al. Hepatocyte growth factor twenty years on: Much more than a growth factor.J Gastroenterol Hepatol. 2011;1:188-202.

[15] Lei X,Wu J,Liu B,et al. Hepatocyte growth factor promoting the proliferation of human eccrine sweat gland epithelial cells is relative to AKT signal channel and β-catenin.Arch Dermatol Res.2012;304(1):23-29.

[16] Ananth KV,Asad M,Prem Kumar N,et al. Evaluation of wound healing potential of bauhinia purpurea leaf extracts in rats r.Indian J Pharm Sci.2010 ;72(1):122-127.

[17] Sanwal R,Chaudhary AK. Wound healing and antimicrobial potential of Carissa spinarum Linn. in albino mice.J Ethnopharmacol.2011;135(3):792-796.

[18] Krause DS, Theise ND, Collector MI, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell.Cell.2001;105:369-377.

[19] Korbing M, Katz RL, Khanna A, et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells.N Engl J Med.2002;346:738-746.

[20] Williams AR,Hare JM.Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease.Cir Res. 2011;109(8): 923-940.