The Differentiation of Mesenchymal Stem Cells into Pacemaker-like Cells_Journal of Biomedical Engineering

Authors：

HUANGChao ,  YANGXiangqun

Department of Anatomy, Institute of Biomedical Engineering, The Second Military Medical University, Shanghai 200433, China;

Corresponding author：

YANGXiangqun, Email: yangxq_sh@126.com

Keywords：

biological pacemaker; bone marrow-derived mesenchymal stem cells; adipose-derived stem cells; pacemaker cells; differentiation

DOI：

10.7507/1001-5515.20160064

Video：

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The biological pacemaker has become a new strategy in the treatment of severe bradycardias, in which a kind of ideal pacemaker cells is a pivotal factor. Here we reviewed the progress in the differentiation of bone-marrow mesenchymal stem cells and adipose-derived stem cells into pacemaker-like cells by means of gene transfer, chemical molecules, co-culture with other cells and specific culture media, and we also analyzed the potential issues to be solved when they are used as seeding cells of biological pacemaker.

Citation： HUANGChao, YANGXiangqun. The Differentiation of Mesenchymal Stem Cells into Pacemaker-like Cells. Journal of Biomedical Engineering, 2016, 33(2): 378-381, 387. doi: 10.7507/1001-5515.20160064 Copy

1.	BAKKER M L, BOINK G J, BOUKENS B J, et al. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells[J]. Cardiovasc Res, 2012, 94(3):439-449.
2.	JUNG J J, HUSSE B, RIMMBACH C, et al. Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells[J]. Stem Cell Reports, 2014, 2(5):592-605.
3.	ROSEN M R, ROBINSON R B, BRINK P R, et al. The road to biological pacing[J]. Nat Rev Cardiol, 2011, 8(11):656-666.
4.	BAKER N, BOYETTE L B, TUAN R S. Characterization of bone marrow-derived mesenchymal stem cells in aging[J]. Bone, 2015, 70:37-47.
5.	FRIEDENSTEIN A J, GORSKAJA J F, KULAGINA N N. Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol, 1976, 4(5):267-274.
6.	HUANG Rulin, CHEN Gang, WANG Wenjin, et al. Synergy between IL-6 and soluble IL-6 receptor enhances bone morphogenetic protein-2/absorbable collagen sponge-induced bone regeneration via regulation of BMPRIA distribution and degradation[J]. Biomaterials, 2015, 67:308-322.
7.	ZHANG Xiaodie, XUE Ke, ZHOU Jia, et al. Chondrogenic differentiation of bone marrowderived stem cells cultured in the supernatant of elastic cartilage cells[J]. Mol Med Rep, 2015, 12(4):5355-5360.
8.	CAO Jiqing, LI Yaqin, LIANG Yingyin, et al. BMP4 inhibits myogenic differentiation of bone marrow-derived mesenchymal stromal cells in mdx mice[J]. Cytotherapy, 2015, 17(9):1213-1219.
9.	ZHANG Yongxing, MA Chao, LIU Xuqiang, et al. Epigenetic landscape in PPARγ2 in the enhancement of adipogenesis of mouse osteoporotic bone marrow stromal cell[J]. Biochim Biophys Acta, 2015, 1852(11):2504-2516.
10.	RUSSO V, YOUNG S, HAMILTON A, et al. Mesenchymal stem cell delivery strategies to promote cardiac regeneration following ischemic injury[J]. Biomaterials, 2014, 35(13):3956-3974.
11.	MINTEER D M, MARRA K G, RUBIN J P. Adipose stem cells:biology, safety, regulation, and regenerative potential[J]. Clin Plast Surg, 2015, 42(2):169-179.
12.	POTAPOVA I, PLOTNIKOV A, LU Zhongju, et al. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers[J]. Circ Res, 2004, 94(7):952-959.
13.	CHENG Jun, ZHANG Zhihui, WEI Lu, et al. Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer create cardiac pacemakers[J]. Cytotherapy, 2012, 14(5):529-539.
14.	WEI Lu, NONG Yaoming, RAN Boli, et al. mHCN4 genetically modified canine mesenchymal stem cells provide biological pacemaking function in complete dogs with atrioventricular block[J]. Pacing Clin Electrophysiol, 2013, 36(9):1138-1149.
15.	ZHOU Yafeng, YANG Xiangjun, LI Hongxia, et al. Genetically-engineered mesenchymal stem cells transfected with human HCN1 gene to create cardiac pacemaker cells[J]. J Int Med Res, 2013, 41(5):1570-1576.
16.	NONG Yaoming, ZHANG Changhai, WEI Lu, et al. In situ investigation of allografted mouse HCN4 gene-transfected rat bone marrow mesenchymal stromal cells with the use of patch-clamp recording of ventricular slices[J]. Cytotherapy, 2013, 15(8):905-919.
17.	YANG Jing, SONG Tao, WU Pan, et al. Differentiation potential of human mesenchymal stem cells derived from adipose tissue and bone marrow to sinus node-like cells[J]. Mol Med Rep, 2012, 5(1):108-113.
18.	LI Yong, LI Bingong, ZHANG Changlie, et al. Effect of NRG-1/ErbB signaling intervention on the differentiation of bone marrow stromal cells into sinus node-like cells[J]. J Cardiovasc Pharmacol, 2014, 63(5):434-440.
19.	宋波,廖斌,于风旭,等.大鼠BMSCs体外诱导培养后连接蛋白40及超极化激活环核苷酸门控阳离子通道4表达的初步研究[J].中国修复重建外科杂志,2012,26(2):146-151.
20.	ZUK P A, ZHU M, MIZUNO H, et al. Multilineage cells from human adipose tissue:implications for cell-based therapies[J]. Tissue Eng, 2001, 7(2):211-228.
21.	HUNG B P, HUTTON D L, KOZIELSKI K L, et al. Platelet-derived growth factor BB enhances osteogenesis of adipose-derived but not bone marrow-derived mesenchymal stromal/stem cells[J]. Stem Cells, 2015, 33(9):2773-2784.
22.	WU S C, HSIAO H F, HO M L, et al. Suppression of discoidin domain receptor 1 expression enhances the chondrogenesis of adipose-derived stem cells[J]. Am J Physiol Cell Physiol, 2015, 308(9):C685-C696.
23.	PATEL S, YIN P T, SUGIYAMA H, et al. Inducing stem cell myogenesis using NanoScript[J]. ACS Nano, 2015, 9(7):6909-6917.
24.	CHEN Lin, CHEN Yuanwei, ZHANG Sheng, et al. MiR-540 as a novel adipogenic inhibitor impairs adipogenesis via suppression of PPARγ[J]. J Cell Biochem, 2015, 116(6):969-976.
25.	BADIMON L, OÑATE B, VILAHUR G. Adipose-derived mesenchymal stem cells and their reparative potential in ischemic heart disease[J]. Rev Esp Cardiol (Engl Ed), 2015, 68(7):599-611.
26.	李勇,李宾公,李哲,等.hHCN2基因转染的脂肪组织来源的成体干细胞可分化为起搏样细胞[J].细胞与分子免疫学杂志,2013,29(9):901-904, 909.
27.	LI Qiong, GUO Zhikun, CHANG Yuqiao, et al. Gata4, Tbx5 and Baf60c induce differentiation of adipose tissue-derived mesenchymal stem cells into beating cardiomyocytes[J]. Int J Biochem Cell Biol, 2015, 66:30-36.
28.	RANGAPPA S, FEN C, LEE E H, et al. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes[J]. Ann Thorac Surg, 2003, 75(3):775-779.
29.	LEE W C, SEPULVEDA J L, RUBIN J P, et al. Cardiomyogenic differentiation potential of human adipose precursor cells[J]. Int J Cardiol, 2009, 133(3):399-401.
30.	CHOI Y S, DUSTING G J, STUBBS S, et al. Differentiation of human adipose-derived stem cells into beating cardiomyocytes[J]. J Cell Mol Med, 2010, 14(4):878-889.
31.	PLANAT-BÉNARD V, MENARD C, ANDRÉ M, et al. Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells[J]. Circ Res, 2004, 94(2):223-229.
32.	PALPANT N J, YASUDA S I, MACDOUGALD O, et al. Non-canonical Wnt signaling enhances differentiation of Sca1⁺/c-kit⁺ adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes[J]. J Mol Cell Cardiol, 2007, 43(3):362-370.
33.	ZHAO Lili, YANG Gongshe, ZHAO Xin. Rho-associated protein kinases play an important role in the differentiation of rat adipose-derived stromal cells into cardiomyocytes in vitro[J]. PLoS One, 2014, 9(12):e115191.
34.	DROMARD C, BARREAU C, ANDRÉ M, et al. Mouse adipose tissue stromal cells give rise to skeletal and cardiomyogenic cell sub-populations[J]. Frontiers in cell and developmental biology, 2014, 2:42.
35.	JUMABAY M, ZHANG Rui, YAO Yucheng, et al. Spontaneously beating cardiomyocytes derived from white mature adipocytes[J]. Cardiovasc Res, 2010, 85(1):17-27.
36.	YAMADA Y, WANG Xiang-di, YOKOYAMA S I, et al. Cardiac progenitor cells in brown adipose tissue repaired damaged myocardium[J]. Biochem Biophys Res Commun, 2006, 342(2):662-670.
37.	LIU Zhiqiang, WANG Haibin, ZHANG Ye, et al. Efficient isolation of cardiac stem cells from brown adipose[J]. J Biomed Biotechnol, 2010, 2010:104296.
38.	陈磊,姬瑞娟,邓子军,等.阻断经典Wnt通路对棕色脂肪干细胞向起搏样细胞分化的作用[J].解剖学杂志,2015,38(2):133-136.

1. BAKKER M L, BOINK G J, BOUKENS B J, et al. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells[J]. Cardiovasc Res, 2012, 94(3):439-449.
2. JUNG J J, HUSSE B, RIMMBACH C, et al. Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells[J]. Stem Cell Reports, 2014, 2(5):592-605.
3. ROSEN M R, ROBINSON R B, BRINK P R, et al. The road to biological pacing[J]. Nat Rev Cardiol, 2011, 8(11):656-666.
4. BAKER N, BOYETTE L B, TUAN R S. Characterization of bone marrow-derived mesenchymal stem cells in aging[J]. Bone, 2015, 70:37-47.
5. FRIEDENSTEIN A J, GORSKAJA J F, KULAGINA N N. Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol, 1976, 4(5):267-274.
6. HUANG Rulin, CHEN Gang, WANG Wenjin, et al. Synergy between IL-6 and soluble IL-6 receptor enhances bone morphogenetic protein-2/absorbable collagen sponge-induced bone regeneration via regulation of BMPRIA distribution and degradation[J]. Biomaterials, 2015, 67:308-322.
7. ZHANG Xiaodie, XUE Ke, ZHOU Jia, et al. Chondrogenic differentiation of bone marrowderived stem cells cultured in the supernatant of elastic cartilage cells[J]. Mol Med Rep, 2015, 12(4):5355-5360.
8. CAO Jiqing, LI Yaqin, LIANG Yingyin, et al. BMP4 inhibits myogenic differentiation of bone marrow-derived mesenchymal stromal cells in mdx mice[J]. Cytotherapy, 2015, 17(9):1213-1219.
9. ZHANG Yongxing, MA Chao, LIU Xuqiang, et al. Epigenetic landscape in PPARγ2 in the enhancement of adipogenesis of mouse osteoporotic bone marrow stromal cell[J]. Biochim Biophys Acta, 2015, 1852(11):2504-2516.
10. RUSSO V, YOUNG S, HAMILTON A, et al. Mesenchymal stem cell delivery strategies to promote cardiac regeneration following ischemic injury[J]. Biomaterials, 2014, 35(13):3956-3974.
11. MINTEER D M, MARRA K G, RUBIN J P. Adipose stem cells:biology, safety, regulation, and regenerative potential[J]. Clin Plast Surg, 2015, 42(2):169-179.
12. POTAPOVA I, PLOTNIKOV A, LU Zhongju, et al. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers[J]. Circ Res, 2004, 94(7):952-959.
13. CHENG Jun, ZHANG Zhihui, WEI Lu, et al. Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer create cardiac pacemakers[J]. Cytotherapy, 2012, 14(5):529-539.
14. WEI Lu, NONG Yaoming, RAN Boli, et al. mHCN4 genetically modified canine mesenchymal stem cells provide biological pacemaking function in complete dogs with atrioventricular block[J]. Pacing Clin Electrophysiol, 2013, 36(9):1138-1149.
15. ZHOU Yafeng, YANG Xiangjun, LI Hongxia, et al. Genetically-engineered mesenchymal stem cells transfected with human HCN1 gene to create cardiac pacemaker cells[J]. J Int Med Res, 2013, 41(5):1570-1576.
16. NONG Yaoming, ZHANG Changhai, WEI Lu, et al. In situ investigation of allografted mouse HCN4 gene-transfected rat bone marrow mesenchymal stromal cells with the use of patch-clamp recording of ventricular slices[J]. Cytotherapy, 2013, 15(8):905-919.
17. YANG Jing, SONG Tao, WU Pan, et al. Differentiation potential of human mesenchymal stem cells derived from adipose tissue and bone marrow to sinus node-like cells[J]. Mol Med Rep, 2012, 5(1):108-113.
18. LI Yong, LI Bingong, ZHANG Changlie, et al. Effect of NRG-1/ErbB signaling intervention on the differentiation of bone marrow stromal cells into sinus node-like cells[J]. J Cardiovasc Pharmacol, 2014, 63(5):434-440.
19. 宋波,廖斌,于风旭,等.大鼠BMSCs体外诱导培养后连接蛋白40及超极化激活环核苷酸门控阳离子通道4表达的初步研究[J].中国修复重建外科杂志,2012,26(2):146-151.
20. ZUK P A, ZHU M, MIZUNO H, et al. Multilineage cells from human adipose tissue:implications for cell-based therapies[J]. Tissue Eng, 2001, 7(2):211-228.
21. HUNG B P, HUTTON D L, KOZIELSKI K L, et al. Platelet-derived growth factor BB enhances osteogenesis of adipose-derived but not bone marrow-derived mesenchymal stromal/stem cells[J]. Stem Cells, 2015, 33(9):2773-2784.
22. WU S C, HSIAO H F, HO M L, et al. Suppression of discoidin domain receptor 1 expression enhances the chondrogenesis of adipose-derived stem cells[J]. Am J Physiol Cell Physiol, 2015, 308(9):C685-C696.
23. PATEL S, YIN P T, SUGIYAMA H, et al. Inducing stem cell myogenesis using NanoScript[J]. ACS Nano, 2015, 9(7):6909-6917.
24. CHEN Lin, CHEN Yuanwei, ZHANG Sheng, et al. MiR-540 as a novel adipogenic inhibitor impairs adipogenesis via suppression of PPARγ[J]. J Cell Biochem, 2015, 116(6):969-976.
25. BADIMON L, OÑATE B, VILAHUR G. Adipose-derived mesenchymal stem cells and their reparative potential in ischemic heart disease[J]. Rev Esp Cardiol (Engl Ed), 2015, 68(7):599-611.
26. 李勇,李宾公,李哲,等.hHCN2基因转染的脂肪组织来源的成体干细胞可分化为起搏样细胞[J].细胞与分子免疫学杂志,2013,29(9):901-904, 909.
27. LI Qiong, GUO Zhikun, CHANG Yuqiao, et al. Gata4, Tbx5 and Baf60c induce differentiation of adipose tissue-derived mesenchymal stem cells into beating cardiomyocytes[J]. Int J Biochem Cell Biol, 2015, 66:30-36.
28. RANGAPPA S, FEN C, LEE E H, et al. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes[J]. Ann Thorac Surg, 2003, 75(3):775-779.
29. LEE W C, SEPULVEDA J L, RUBIN J P, et al. Cardiomyogenic differentiation potential of human adipose precursor cells[J]. Int J Cardiol, 2009, 133(3):399-401.
30. CHOI Y S, DUSTING G J, STUBBS S, et al. Differentiation of human adipose-derived stem cells into beating cardiomyocytes[J]. J Cell Mol Med, 2010, 14(4):878-889.
31. PLANAT-BÉNARD V, MENARD C, ANDRÉ M, et al. Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells[J]. Circ Res, 2004, 94(2):223-229.
32. PALPANT N J, YASUDA S I, MACDOUGALD O, et al. Non-canonical Wnt signaling enhances differentiation of Sca1⁺/c-kit⁺ adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes[J]. J Mol Cell Cardiol, 2007, 43(3):362-370.
33. ZHAO Lili, YANG Gongshe, ZHAO Xin. Rho-associated protein kinases play an important role in the differentiation of rat adipose-derived stromal cells into cardiomyocytes in vitro[J]. PLoS One, 2014, 9(12):e115191.
34. DROMARD C, BARREAU C, ANDRÉ M, et al. Mouse adipose tissue stromal cells give rise to skeletal and cardiomyogenic cell sub-populations[J]. Frontiers in cell and developmental biology, 2014, 2:42.
35. JUMABAY M, ZHANG Rui, YAO Yucheng, et al. Spontaneously beating cardiomyocytes derived from white mature adipocytes[J]. Cardiovasc Res, 2010, 85(1):17-27.
36. YAMADA Y, WANG Xiang-di, YOKOYAMA S I, et al. Cardiac progenitor cells in brown adipose tissue repaired damaged myocardium[J]. Biochem Biophys Res Commun, 2006, 342(2):662-670.
37. LIU Zhiqiang, WANG Haibin, ZHANG Ye, et al. Efficient isolation of cardiac stem cells from brown adipose[J]. J Biomed Biotechnol, 2010, 2010:104296.
38. 陈磊,姬瑞娟,邓子军,等.阻断经典Wnt通路对棕色脂肪干细胞向起搏样细胞分化的作用[J].解剖学杂志,2015,38(2):133-136.

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