Effects of bone marrow mesenchymal stem cells and benefiting-Qi nourishing-Yin and dissolving-congestion prescription on lower extremity arterial restenosis in model dogs with diabetes mellitus

doi:10.3969/j.issn.2095-4344.2014.18.015

Abstract

Abstract:

BACKGROUND: At present, a great quantity of research has shown the effectiveness of traditional Chinese medicine and bone marrow mesenchymal stem cells for vascular restenosis. However, studies concerning their combined application to restenosis after percutaneous transluminal angioplasty with diabetes mellitus are presently lacking.
OBJECTIVE: To observe the effects of combined application of bone marrow mesenchymal stem cells and benefiting-Qi nourishing-Yin and dissolving-congestion prescription on restenosis after percutaneous transluminal angioplasty in dogs with diabetes mellitus.
METHODS: A dog model of vascular restenosis with diabetes mellitus was established by balloon injury of femoral artery and intravenous injection of alloxan. After successful model induction, 22 dog models were randomly divided into three groups: model group (n=6), treatment with Chinese medicine (n=8), and combined treatment with bone marrow mesenchymal stem cells and Chinese medicine (n=8). Serum vascular endothelial growth factor levels were measured using enzyme-linked immunosorbent assay preoperatively and at 1, 2, 4 and 8 weeks postoperation. Samples of vessels were taken to conduct pathomorphological observation and quantitative analysis of proliferation degree. Tissues, including heart, liver, kidney and pancreatic gland, were collected to evaluate the safety of stem cell transplantation using hematoxylin-eosin staining at 8 weeks postoperation.
RESULTS AND CONCLUSION: Serum vascular endothelial growth factor levels began to increase at 1 week postoperation in the Chinese medicine group and combined treatment group, at 4 weeks postoperation in the model group compared with preoperation (P < 0.05). At all time points, serum vascular endothelial growth factor levels were highest in the combined treatment group, but lowest in the model group (P < 0.05). Quantitative analysis of vascular proliferation demonstrated that at 8 weeks postoperation, new intimal area, new intimal/medial areas and stenosis rate were highest in the model group, but lowest in the combined treatment group at 8 weeks postoperation (P < 0.05). Safety assessment of stem cell transplantation showed morphological structures of the heart, liver, kidneys and pancreas were normal, no necrosis. In a word, the effects of the combined application of bone marrow mesenchymal stem cells and benefiting-Qi nourishing-Yin and dissolving-congestion prescription were much pronounced in preventing restenosis after percutaneous transluminal angioplasty in dogs with diabetes mellitus rather than single therapy of Chinese medicine. It is a safe and effective treatment to prevent vascular restenosis after percutaneous transluminal angioplasty in dogs with diabetes mellitus.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: stem cells, mesenchymal stem cells, vascular endothelial growth factors, drugs, Chinese herbal

CLC Number:

R318

Cheng Xue, Wang Yi-zhong, Ding Ming-chao, Cui Xiao-lan, Wang Bin, Wang Jia, Shi Han,. Effects of bone marrow mesenchymal stem cells and benefiting-Qi nourishing-Yin and dissolving-congestion prescription on lower extremity arterial restenosis in model dogs with diabetes mellitus[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(18): 2872-2879.

Figures/Tables 4

References

[1] Min SK, Kenagy RD, Clowes AW. Induction of vascular atrophy as a novel approach to treating restenosis. A review. J Vasc Surg. 2008;47(3):662-670.
[2] Liistro F, Porto I, Angioli P, et al. Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation. 2013;128(6): 615-621.
[3] 张文利,黄定. PCI术后冠状动脉再狭窄机制及防治研究进展[J].中国循证心血管医学杂志,2011,3(2):154-156.
[4] 韩劲草,刘喜林,顾海波,等.同强度不同波长β射线培养液对兔血管平滑肌细胞生长的影响[J].中国医药导刊,2004,6(1):39-40, 44.
[5] Niccoli G, Sgueglia GA, Montone RA, et al. Evolving management of patients treated by drug-eluting stent: Prevention of late events. Cardiovasc Revasc Med. 2014.
[6] Kallidonis PS, Georgiopoulos IS, Kyriazis ID, et al. Drug-eluting metallic stents in urology. Indian J Urol. 2014; 30(1):8-12.
[7] Bradshaw AC, Baker AH. Gene therapy for cardiovascular disease: perspectives and potential. Vascul Pharmacol. 2013;58(3):174-181.
[8] Chen LJ, Lim SH, Yeh YT, et al. Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci. 2012;19(1):79.
[9] Vassalli G, Vanderheyden M, Renders F, et al. Bone marrow stem cell therapy for cardiac repair: challenges and perspectives. Minerva Cardioangiol. 2007;55(5):659-667.
[10] Knight MN, Hankenson KD. Mesenchymal Stem Cells in Bone Regeneration. Adv Wound Care (New Rochelle). 2013;2(6): 306-316.
[11] Ikebe C, Suzuki K. Mesenchymal Stem Cells for Regenerative Therapy: Optimization of Cell Preparation Protocols. Biomed Res Int. 2014;2014:951512.
[12] Harada M, Qin Y, Takano H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med. 2005;11(3): 305-311.
[13] 杜冠华,张均田.丹参现代研究概况与进展(续一)[J].医药导报, 2004,23(6):355-360.
[14] 林蓉,刘俊田,李旭,等.川芎嗪对血管内皮细胞损伤的保护作用[J].中国药理学与毒力学杂志,2000,14(6):425.
[15] 李秋梅.益气活血解毒方和血府逐瘀胶囊对家兔PTA术后再狭窄的防治作用研究[D].北京中医药大学,2004.
[16] 侯霄雷,李白翎,赵雷,等. 血府逐瘀胶囊对急性心肌梗死再灌注后心肌及内皮素-1、一氧化氮/一氧化氮合酶体系影响的实验研究[J].中西医结合学报,2008,6(4):381-386.
[17] 中华人民共和国科学技术部.关于善待实验动物的指导性意见. 2006-09-30.
[18] Jelodar G, Razmi N, Gholampour V. Arginase alteration in the reproductive system of alloxan-diabetic dogs. J Reprod Dev. 2007;53(2):317-321.
[19] Manhiani MM, Cormican MT, Brands MW. Chronic sodium-retaining action of insulin in diabetic dogs. Am J Physiol Renal Physiol. 2011;300(4):F957-965.
[20] 周贤用,傅红兴,刘云西,等. 1例Beagle犬的糖尿病建模分析[J].中国医药科学,2011,1(15):46-47.
[21] 王立梅,崔晓兰,丁明超,等. 自体骨髓间充质干细胞经动脉介入移植治疗犬糖尿病[J].中国组织工程研究,2012,16(19): 3545-3550.
[22] Won KB, Chang HJ, Hong SJ, et al. Prognostic usefulness of metabolic syndrome compared with diabetes in Korean patients with critical lower limb ischemia treated with percutaneous transluminal angioplasty. Yonsei Med J. 2014;55(1):46-52.
[23] Rekik S, Brunet J, Bayet G, et al. Percutaneous management of lower limb ischemia after the use of vascular closure devices. Can J Cardiol. 2013;29(11):1448-1453.
[24] Naleem A, Zaman A, Low K, et al. Functional lengths of the lower limb arterial tree measured by CT angiography centreline analysis: implications for catheter lengths in peripheral angioplasty. Surg Radiol Anat. 2013. [Epub ahead of print]
[25] Forte A, Rinaldi B, Sodano L, et al. Stem cell therapy for arterial restenosis: potential parameters contributing to the success of bone marrow-derived mesenchymal stromal cells. Cardiovasc Drugs Ther. 2012;26(1):9-21.
[26] Oda Y, Tani K, Kanei T, et al. Characterization of neuron-like cells derived from canine bone marrow stromal cells. Vet Res Commun. 2013;37(2):133-138.
[27] Zhang W, Zhang F, Shi H, et al. Comparisons of rabbit bone marrow mesenchymal stem cell isolation and culture methods in vitro. PLoS One. 2014;9(2):e88794.
[28] Li Q, Wang Z. Influence of mesenchymal stem cells with endothelial progenitor cells in co-culture on osteogenesis and angiogenesis: an in vitro study. Arch Med Res. 2013; 44(7):504-513.
[29] Kisiel AH, Mcduffee LA, Masaoud E, et al. Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum. Am J Vet Res. 2012;73(8): 1305-1317.
[30] Volk SW, Wang Y, Hankenson KD. Effects of donor characteristics and ex vivo expansion on canine mesenchymal stem cell properties: implications for MSC-based therapies. Cell Transplant. 2012;21(10):2189- 2200.
[31] Sauerzweig S, Munsch T, Lessmann V, et al. A population of serum deprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells. Exp Cell Res. 2009;315(1):50-66.
[32] Hall SR, Jiang Y, Leary E, et al. Identification and isolation of small CD44-negative mesenchymal stem/progenitor cells from human bone marrow using elutriation and polychromatic flow cytometry. Stem Cells Transl Med. 2013;2(8):567-578.
[33] Chan AK, Heathman TR, Coopman K, et al. Multiparameter flow cytometry for the characterisation of extracellular markers on human mesenchymal stem cells. Biotechnol Lett. 2014;36(4):731-741.
[34] Feisst V, Brooks AE, Chen CJ, et al. Characterization of mesenchymal progenitor cell populations directly derived from human dermis. Stem Cells Dev. 2014;23(6):631-642.
[35] 廖耿,舒崖清,胡学强. 丹红注射液对家兔颈动脉PTA术后内膜增生及bFGF、TF表达的影响[J].中华神经医学杂志,2011,10(7): 673-678.
[36] Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987; 235(4787):442-447.
[37] van der Zee R, Murohara T, Luo Z, et al. Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation. 1997;95(4):1030-1037.
[38] Reyes M, Lund T, Lenvik T, et al. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 2001;98(9):2615-2625.
[39] Galmiche MC, Koteliansky VE, Briere J, et al. Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway. Blood. 1993;82(1):66-76.
[40] Oswald J, Boxberger S, Jorgensen B, et al. Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 2004;22(3):377-384.
[41] Silva GV, Litovsky S, Assad JA, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005;111(2):150-156.