Chinese medicine induces differentiation of bone marrow mesenchymal stem cells into cardiomyocytes

doi:10.3969/j.issn.2095-4344.2014.01.026

Abstract

Abstract:

BACKGROUND: Traditional Chinese medicine shares wide application in clinical treatment because of its high security. At present, a lot of studies have been reported, in which, traditional Chinese medicine or monomers are used for in vitro differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells.
OBJECTIVE: To summarize and analyze the research progress of Chinese medicine to induce the differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells and to looking prospect for its application.
METHODS: CNKI database was searched for the articles about Chinese medicine-induced differentiation of bone marrow mesenchymal stem cells into cardiomyocytes, published from January 2001 to January 2013. The key words were “Chinese medicine, bone marrow mesenchymal stem cells, cardiomyocyte” in Chinese and “bone marrow mesenchymal stem cells, myocardial cells” in English. Obsolete or repetitive articles were excluded. Finally, 36 articles were included in result analysis.
RESULTS AND CONCLUSION: Different Chinese medicine formulations were used as inducers to induce differentiation of bone marrow mesenchymal stem cells into cardiomyocytes, including Panax notoginseng saponins, salvianolic acid B, Jiawei Danshen Yin, icariin, astragaloside. Then, the induced cells were examined by immunohistochemistry and reverse transcription-PCR. The results showed that the induced cells were positive for Desmin, cardiac troponin I and major histocompatibility complex. Positive cells were fusiform and fibroblast-like morphology, which indicates a role in promoting proliferation and differentiation. These findings show that Chinese medicine-induced differentiation of bone marrow mesenchymal stem cells into cardiomyocytes has become a worldwide research hotspot, providing a theoretical basis for clinical treatment of ischemic heart diseases.

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: stem cells, bone marrow, mesenchymal stem cells, drugs, Chinese herbal, myocytes, cardiac, cell differentiation

CLC Number:

R318

Wang Yan, Wang Hai-ping, Lv Yang . Chinese medicine induces differentiation of bone marrow mesenchymal stem cells into cardiomyocytes[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(1): 155-160.

Figures/Tables 3

2.2 黄芪甲苷(Astragaloside) 黄芪甲苷来源于黄芪类植物的根，具有增强免疫力、增加能量、抗疲劳、抑突变等作用，用于心气虚损、血脉淤阻之病毒性心肌炎、心功能不全及脾虚湿困之肝炎。黄芪甲苷诱导骨髓间充质干细胞分化为心肌细胞已经进行了一些研究，冼绍祥等[16]采用密度梯度离心和贴壁培养法分离大鼠骨髓间充质干细胞，反复传代及纯化后，取第8代骨髓间充质干细胞进行分组诱导。诱导后继续培养4周，免疫组化结果显示诱导后骨髓间充质干细胞表达肌细胞纤维蛋白(Desmin)、心肌肌钙蛋白I(cTnI)；RT-PCR结果显示诱导后骨髓间充质干细胞表达主要组织相容性复合体A(A-MHC)和主要组织相容性复合体B(B-MHC)。另外，黄芪可升高肥大心肌细胞钙瞬变波幅，表明黄芪注射液能从整体水平改善心肌收缩舒张功能[17]。证明黄芪甲苷可在体外诱导大鼠骨髓间充质干细胞定向分化为心肌样细胞。黄芪皂甙(astraga loside,AS)同为黄芪的有效成分，并有研究表明其具有抗氧化作用，能刺激骨髓基质细胞的增殖，促进其分泌白细胞介素1和肿瘤坏死因子α可能与其刺激骨髓间充质干细胞微环境中分泌细胞因子及活性较高的调控因子或协同生长因子有关，而黄芪甲苷诱导骨髓间充质干细胞转化为心肌样细胞可能与其抗氧化及刺激骨髓间充质干细胞分泌某些诱导细胞因子有关。此后，杨庆有等[18]研究给日本大耳白兔灌胃黄芪药液，10 d后颈动脉采血制备黄芪含药血清。分离SD大鼠骨髓间充质干细胞进行传代培养，用黄芪含药血清诱导分化，免疫组化法检测诱导后细胞心肌肌钙蛋白T(cTnT)和肌细胞纤维蛋白(Desmin)表达阳性，RT-PCR反应测定主要组织相容性复合体A(A-MHC)和主要组织相容性复合体B(B-MHC)阳性。表明黄芪含药血清可诱导骨髓间充质干细胞分化为心肌样细胞[19]。"

References

[1] Fukuhara S, Tomita S, Yamashiro S,et al. Direct cell-cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro.J Thorac Cardiovasc Surg. 2003;125(6):1470-1480.

[2] Melo LG, Pachori AS, Kong D,et al. Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism. Circulation. 2004 ;109(20):2386-2393.

[3] 张近宝,顾春虎,刘维永,等.犬骨髓间充质干细胞可诱导分化为组织工程瓣间质种子细胞[J].心脏杂志,2006,18(5):489-491,495.

[4] 程芮,王士雯,曹丰,等. 5-氮胞苷浓度对体外骨髓间充质干细胞诱导分化为心肌样细胞的影响[J].中华老年多器官疾病杂志, 2005,4(3):196-199,220.

[5] 李国庆,张卫泽,马凌,等.5-氮胞苷对脂肪间充质干细胞向心肌样细胞诱导分化的影响[J]. 西北国防医学杂志,2009,30(5): 357- 360.

[6] 王欢,杨曦,魏琴,等. 5-氮胞苷诱导大鼠骨髓间充质干细胞向心肌细胞分化的研究[J].新疆医科大学学报,2012,35(12): 1590- 1594.

[7] 何晓青,陈敏生,刘世明,等. FGF-2 诱导骨髓间充质干细胞获得心肌分化表型[J].中国现代医学杂志,2009,19(23):3580-3583.

[8] 刘建华,陈运贤,张祥忠,等.碱性成纤维细胞生长因子对大鼠骨髓间质干细胞诱导分化为心肌细胞的影响[J].中山大学学报:医学科学版,2006,23(z1):10-13.

[9] 王海萍,张雷,王浩宇,等.催产素体外诱导大鼠骨髓间充质干细胞向心肌细胞分化[J].基础医学与临床,2011,31(11):1273-1277.

[10] 兰萍,刘颖,李小波,等. 红花注射液治疗肺心病心力衰竭疗效观察[J].时珍国医国药,2010,21(4):1026.

[11] 王秀力,王洁,宫海滨.心肌微环境对诱导大鼠骨髓间充质干细胞分化为心肌样细胞的影响[J].现代生物医学进展,2008,8(12): 2419-2415.

[12] 孔晓丹,曲鹏,王彦,等.三七皂甙诱导骨髓基质细胞分化为心肌样细胞的实验研究[J].中国心血管病研究杂志,2005,3(7):528-530.

[13] 李志泉,冼绍祥,汪朝晖,等.三七总皂苷对骨髓间充质干细胞增殖和向心肌样细胞分化的影响[J].广州中医药大学学报,2007, 24(6): 470-475.

[14] 宋清,张晓文,卢新政,等.参三七皂苷Rg1预适应对5-氮胞苷诱导大鼠骨髓间充质干细胞向心肌细胞转化的干预[J].中国组织工程研究与临床康复,2007,11(24):4693-4697.

[15] 汪朝晖,冼绍祥,杨忠奇,等.人参总皂甙诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2006, 23(2):100-103.

[16] 冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2007, 24(1):37-40.

[17] 孙娅楠,农一兵,林谦.黄芪及丹参对肥大心肌细胞肌浆网钙转运干预作用研究[J].中华中医药杂志,2012,27(1):175-180.

[18] 杨庆有,冼绍祥,孙慧茹,等.黄芪含药血清诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].辽宁中医杂志,2008,35(6): 832-834.

[19] 陈旭.黄芪注射液预处理对大鼠骨髓间充质干细胞定向分化的诱导作用研究[J].吉林中医药,2012,32(9):921-923.

[20] 谢玲玲.淫羊藿苷诱导骨髓间充质干细胞分化心肌样细胞的实验研究[D].广州:广州中医药大学,2008.

[21] 刘韶英.淫羊藿苷对骨髓间充质干细胞增殖及向心肌细胞分化的影响[D].北京:北京中医药大学,2008.

[22] 孙晓冬,董韬,于宏伟,等.淫羊藿苷体外诱导小鼠胚胎干细胞分化为心肌细胞[J].解剖科学进展,2011,17(2):124-127.

[23] 华声瑜,范英昌,马轶文,等.丹酚酸B对大鼠骨髓间充质干细胞分化过程中Desmin、α-actinmRNA表达的影响[J].天津中医药, 2009,26(2):145-148.

[24] 徐秀梅,郭茂娟,赵旭,等.丹酚酸B体外诱导骨髓间充质干细胞向心肌样细胞分化的实验研究[J].时珍国医国药,2008,19(3): 574-576.

[25] 南亚昀,李庆雯,谭俊珍,等.丹酚酸B预处理EPCs联合BMSc移植对AMI大鼠心功能的影响[J].天津中医药,2009,26(1):60-62.

[26] 陈嘉,孙京臣,邹移海,等.丹酚酸B诱导骨髓间充质干细胞向心肌样细胞分化[J].第四军医大学学报,2007,28(23):2152-2155.

[27] 谢静.加味丹参饮联合BMSCs移植对IRI大鼠心肌细胞的保护作用及机制研究[D].长沙:湖南中医药大学,2012.

[28] 赵鸿.加味丹参饮含药血清体外诱导的BMSCs移植对心肌IRI模型大鼠血管新生影响的研究[D].长沙:湖南中医药大学,2012.

[29] 王明宁,林洪,胡琳,等.香丹注射液对大鼠骨髓间充质干细胞的增殖作用[J].华西药学杂志,2007,22(3):304-305.

[30] 曾意荣,樊粤光,刘红,等.补肾活血中药对大鼠骨髓间充质干细胞体外增殖的影响[J].中药新药与临床药理,2007,18(2):93-96.

[31] 张明雪,何伟,顾平,等.益气活血中药复方对CVB3 病毒性心肌炎心肌细胞actin、Cx43表达及GJIC 功能的影响[J].中国中西医结合杂志,2010,30(8):880-883.

[32] 夏文杰,陈振光,张丽蓉,等.隐丹参酮诱导骨髓间质干细胞分化为神经元样细胞的实验研究[J].中国中西医结合杂志,2002,22(12): 921-924.

[33] 董燕湘,董晓先,何慧华,等.大鼠骨髓间质干细胞用中药绞股蓝诱导为神经细胞的研究[J].中华神经科杂志,2003,36(5):355-358.

[34] 李玉冰.丹参酮Ⅱa、川芎嗪联合体外诱导BMSCs分化为心肌样细胞的研究[D].长沙:湖南中医药大学,2011.

[35] 项鹏,夏文杰,王连荣,等.丹参注射液诱导间质干细胞分化为神经元样细胞[J].中山医科大学学报,2001,22(5):321-324.

[36] 肖庆忠,温冠媚,李浩威,等.麝香组分诱导成年大鼠骨髓间质干细胞体外定向分化为神经元样细胞的能力[J].中山医科大学学报, 2002,23(6):405-408.