Umbilical cord mesenchymal stem cell transplantation for treatment of diabetic lower limb vascular disease

doi:10.3969/j.issn.2095-4344.2014.23.011

Abstract

Abstract:

BACKGROUND: Compared with bone marrow and autologous peripheral blood stem cells, umbilical cord mesenchymal stem cells are characterized as more primitive, more powerful amplification and lower immunogenicity, no ethical problems, which are more important to the elderly patients with diabetes mellitus.

OBJECTIVE: To evaluate the efficacy and safety of umbilical cord mesenchymal stem cells transplantation in the treatment of the elderly patients with diabetic lower limb vascular disease.

METHODS: Fifty-six elderly patients with diabetic lower limb vascular disease were randomly divided into observation group and control group. The control group was treated with conventional therapy, while the observation group was treated with umbilical cord mesenchymal stem cells transplantation.

RESULTS AND CONCLUSION: Observation group showed a higher efficiency than the control group, with significant difference (P < 0.05). After treatment, foot skin temperature, transcutaneous oxygen pressure, and ankle brachial index were all improved in both two groups, and the ankle brachial index showed a better value in the observation group (P < 0.05). There were no significant adverse reactions in the two groups. Umbilical cord mesenchymal stem cells transplantation is a simple, safe and effective therapy for the elderly patients with diabetic lower limb vascular disease, with better short-term curative effect.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: umbilical cord, mesenchymal stem cell transplantation, diabetes mellitus, type 2, diabetic angiopathies

CLC Number:

R394.2

Li Xiao-ling, Zhu Lv-yun, Song Guang-yao, Jia Li-jing, Yang Shao-ling, Hu Li-ye. Umbilical cord mesenchymal stem cell transplantation for treatment of diabetic lower limb vascular disease[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(23): 3670-3675.

Figures/Tables 5

References

[1] 马晓兰,沈建国.糖尿病合并外周动脉疾病的研究进展[J].中国老年学杂志, 2012,32(23): 5350-5354.
[2] 谷涌泉,张建,赵峰,等.老年人糖尿病下肢动脉粥样硬化临床特点及相关因素的研究[J].中华老年多器官疾病杂志, 2007,6(5): 325-328.
[3] 谷涌泉,张建,汪忠镐,等.糖尿病性下肢缺血的外科治疗[J].中华糖尿病杂志, 2004,12(5):328-331.
[4] 廖传军,姜涛,杨宝钟.糖尿病对血管重建治疗慢性重症下肢缺血的影响[J].中国普通外科杂志, 2011,20(6): 575-578.
[5] Gu YQ.Determination of amputation level in ischaemic lower limbs.ANZ J Surg. 2004;74(1-2):31-33.
[6] Hang D, Wang Q, Guo C,et al.Treatment of osteonecrosis of the femoral head with VEGF165 transgenic bone marrow mesenchymal stem cells in mongrel dogs.Cells Tissues Organs. 2012;195(6):495-506.
[7] Putman DM, Liu KY, Broughton HC,et al.Umbilical cord blood-derived aldehyde dehydrogenase-expressing progenitor cells promote recovery from acute ischemic injury.Stem Cells. 2012;30(10):2248-2260.
[8] Brenes RA, Jadlowiec CC, Bear M,et al.Toward a mouse model of hind limb ischemia to test therapeutic angiogenesis.J Vasc Surg. 2012;56(6):1669-1679.
[9] Smadja D, Silvestre JS, Lévy BI.Genic and cellular therapy for peripheral arterial diseases.Transfus Clin Biol. 2013;20(2): 211-220.
[10] Altaner C, Altanerova V, Cihova M,et al.Characterization of mesenchymal stem cells of "no-options" patients with critical limb ischemia treated by autologous bone marrow mononuclear cells.PLoS One. 2013;8(9):e73722.
[11] Mohammadzadeh L, Samedanifard SH, Keshavarzi A,et al. Therapeutic outcomes of transplanting autologous granulocyte colony-stimulating factor-mobilised peripheral mononuclear cells in diabetic patients with critical limb ischaemia.Exp Clin Endocrinol Diabetes. 2013;121(1):48-53.
[12] Li Q, Yao D, Ma J,et al.Transplantation of MSCs in combination with netrin-1 improves neoangiogenesis in a rat model of hind limb ischemia.J Surg Res. 2011;166(1): 162-169.
[13] Lu D, Chen B, Liang Z,et al.Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial.Diabetes Res Clin Pract. 2011;92(1):26-36.
[14] Gabr H, Hedayet A, Imam U,et al.Limb salvage using intramuscular injection of unfractionated autologous bone marrow mononuclear cells in critical limb ischemia: a prospective pilot clinical trial.Exp Clin Transplant. 2011;9(3): 197-202.
[15] Wang H, Qiu X, Ni P,et al.Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats.Int J Mol Med. 2014;33(2):263-270.
[16] Zhang HC, Liu XB, Huang S,et al.Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo.Stem Cells Dev. 2012;21(18):3289-3297.
[17] Duya P, Bian Y, Chu X,et al.Stem cells for reprogramming: could hUMSCs be a better choice.Cytotechnology. 2013;65(3): 335-345.
[18] Chen Y, Yu B, Xue G,et al.Effects of storage solutions on the viability of human umbilical cord mesenchymal stem cells for transplantation.Cell Transplant. 2013;22(6):1075-1086.
[19] Cabrera C, Carriquiry G, Pierinelli C,et al.The role of biologically active peptides in tissue repair using umbilical cord mesenchymal stem cells.Ann N Y Acad Sci. 2012;1270: 93-97.
[20] 刘阁玲,李伟娟,俞芳,等.自体骨髓干细胞移植治疗糖尿病合并下肢缺血性疾病20例报告[J].军事医学科学院院刊, 2007, 31(2): 196-197.
[21] 王爱红,许樟荣.干细胞移植——治疗糖尿病缺血性下肢血管病变的新手段[J].国外医学:内分泌学分册, 2005, 25(6): 430-432.
[22] 刘慧纯,张培培,王世民,等.脐带间充质干细胞移植治疗大鼠脑缺血损伤[J].中国组织工程研究,2012,16(19): 3471-3475.
[23] 吴石白, 关小宏.干细胞移植治疗糖尿病下肢动脉缺血性病变及糖尿病足的现状与未来[J].空军总医院学报,2008,24(4): 235-237.
[24] Tateishi-Yuyama E, Matsubara H, Murohara T,et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial.Lancet. 2002;360(9331): 427-435.
[25] Liew A, O'Brien T.Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia.Stem Cell Res Ther. 2012;3(4):28.
[26] Hart CA, Tsui J, Khanna A,et al.Stem cells of the lower limb: their role and potential in management of critical limb ischemia.Exp Biol Med (Maywood). 2013;238(10):1118-1126.
[27] 王广宇,朱旅云,马利成,等.干细胞移植治疗糖尿病足[J].中国组织工程研究,2013,17(1):173-180.
[28] Setacci C, de Donato G, Teraa M, et al.Chapter IV: Treatment of critical limb ischaemia.Eur J Vasc Endovasc Surg. 2011;42 Suppl 2:S43-59.
[29] Napoli C, Williams-Ignarro S, de Nigris F,et al.Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb.Proc Natl Acad Sci U S A. 2005;102 (47): 17202-17206.
[30] 樊明世,杨晓凤,吴雁翔,等.人脐带间充质干细胞移植改善糖尿病兔下肢缺血[J].中国组织工程研究与临床康复, 2011,15(1): 33-36.
[31] 吴春朋,张潜,方宁,等.骨髓间充质干细胞移植促进糖尿病大鼠后肢缺血血管的新生[J].中国组织工程研究, 2012,16(1): 76-80.
[32] 杨辉,邓显,施森,等.自体外周血干细胞移植联合血管腔内成形术治疗下肢缺血性疾病的疗效观察[J].实用医院临床杂志, 2012, 9(5): 96-98.
[33] 谷涌泉,郭连瑞,张建.自体干细胞移植治疗下肢缺血[J].临床外科杂志, 2006,14(5): 318-320.
[34] 谷涌泉,齐立行,郭连瑞,等.自体骨髓干细胞移植治疗严重下肢缺血5例[J].中国康复医学杂志, 2004,19(9): 687-688.
[35] 杨娥,郑红梅,边竞.自体骨髓干细胞移植治疗糖尿病足的监护2例[J].中国实用护理杂志, 2005,21(9): 18-19.
[36] Li Q, Yao D, Ma J,et al.Transplantation of MSCs in combination with netrin-1 improves neoangiogenesis in a rat model of hind limb ischemia.J Surg Res. 2011;166(1): 162-169.
[37] 孔霞,郑飞,郭凌郧,等.VEGF通过细胞外信号调节激酶途径促进骨髓源间充质干细胞的增殖[J].中国实验血液学杂志, 2010, 18(5): 1292-1296.
[38] 彭锦,迟路湘.细胞间直接接触对骨髓间充质干细胞分化为血管内皮细胞的作用[J]. 第三军医大学学报, 2010,32(21): 2286-2289.
[39] 付阿丹,邓琳.老年糖尿病周围血管病变患者外周血干细胞采集效果影响因素分析[J].细胞与分子免疫学杂志,2011, 27(7): 799-802.
[40] 李晓玲,朱旅云,赵芳.脐带Wharton’s Jelly中间充质干细胞的生物学特性[J].中国组织工程研究与临床康复,2011,15(32):5979- 5982.
[41] 吴春朋,张潜,方宁,等.骨髓间充质干细胞移植促进糖尿病大鼠后肢缺血血管的新生[J].中国组织工程研究, 2012,16(1): 76-80.
[42] Wang HS, Hung SC, Peng ST,et al.Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord.Stem Cells. 2004;22(7):1330-1337.
[43] Setacci C, de Donato G, Teraa M, et al.Chapter IV: Treatment of critical limb ischaemia.Eur J Vasc Endovasc Surg. 2011;42 Suppl 2:S43-59.
[44] Madonna R, Pizzi SD, Tartaro A,et al.Transplantation of Mesenchymal Cells Improves Peripheral Limb Ischemia in Diabetic Rats.Mol Biotechnol. 2014. [Epub ahead of print]
[45] Powell RJ, Comerota AJ, Berceli SA,et al. Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia.J Vasc Surg. 2011;54(4): 1032-1041.
[46] Tepper OM, Galiano RD, Capla JM,et al.Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures.Circulation. 2002;106(22):2781-2786.
[47] 李鹏,周长勇,尹磊,等.低氧对人脐带间充质干细胞活性和内皮分化能力的影响及VEGF的干预作用[J].中南大学学报(医学版), 2013,38(4):329-340.
[48] 侯跃龙,李彤,张臣,等. CoCl2缺氧处理对脐带间充质干细胞促血管生长因子表达的影响[J].心脏杂志,2011, 23(1): 59-64.
[49] 王惠荟,吕静雅,胡雅楠,等. VEGF通过调节黏着斑促进间充质干细胞的黏附及铺展[J].中国细胞生物学学报, 2012, 34(10): 967-975.
[50] 陈明卫,李燕萍,唐益忠,等.不同来源和移植途径的自体干细胞治疗糖尿病缺血性下肢血管病变的随机对照研究[J].中华临床医师杂志:电子版, 2013, 7(14): 6418-6423.