Progress of Stem Cell Treatment of Pulmonary Arterial Hypertension_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANGChao-hui ,  ANYong

Department of Cardiothoracic Surgery, Children's Hospital, Chongqing Medical University, Chongqing 400014, R. P. China;

Corresponding author：

ANYong, Email: incavnate@126.com

Keywords：

Pulmonary arterial hypertension; Stem cells; Treatment

DOI：

10.7507/1007-4848.20160068

Video：

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Abstract Full text Figures/Tables Video References Cited by

Pulmonary arterial hypertension is a kind of intractable disease which threatens human health severely. The results of operation are unsatisfactory. Clinical drug therapy is the major treatment which aims to relieve symptoms, improve the quality of life, and prevent the disease from progressing. Over the last several years, the studies of stem cells provide a new direction for the treatment of pulmonary arterial hypertension. It's demonstrated that the therapeutic effects of stem cells are better than that of the traditional methods. With the deepening of the researches, the therapy of stem cells is more and more compelling. The therapy of stem cells for pulmonary arterial hypertension is reviewed in this paper.

Citation： WANGChao-hui, ANYong. Progress of Stem Cell Treatment of Pulmonary Arterial Hypertension. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(3): 294-298. doi: 10.7507/1007-4848.20160068 Copy

1.	Kovacs G, Berghold A, Scheidl S, et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J, 2009, 34(4): 888-894.
2.	Shimoda LA, Laurie SS. Vascular remodeling in pulmonary hyper-tension. J Mol Med (Berl), 2013, 91(3): 297-309.
3.	Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol, 2009, 54(1 Suppl): S55-S66.
4.	Pullamsetti SS, Schermuly R, Ghofrani A, et al. Novel and emerging therapies for pulmonary hypertension. Am J Respir Crit Care Med, 2014, 189(4): 394-400.
5.	Aschermann M, Jansa P. Drug therapy of pulmonary arterial hypertension in 2014. Vnitr Lek, 2014, 60(4): 282-288.
6.	张清友, 杜军保. 肺动脉高压的治疗现状与进展. 临床儿科杂志, 2010, 28(7): 607-610.
7.	Majka S, Burnham E, Stenmark KR. Cell-based therapies in pulmo-nary hypertension: who, what, and when? Am J Physiol Lung Cell Mol Physiol, 2011, 301(1): L9-L11.
8.	Foster WS, Suen CM, Stewart DJ. Regenerative cell and tissue-based therapies for pulmonary arterial hypertension. Can J Cardiol, 2014, 30(11): 1350-1360.
9.	Angelini A, Castellani C, Ravara B, et al. Stem-cell therapy in an experimental model of pulmonary hypertension and right heart failure: role of paracrine and neurohormonal milieu in the remode-ling process. J Heart Lung Transplant, 2011, 30(11): 1281-1293.
10.	Yang JX, Pan YY, Zhao YY, et al. Endothelial progenitor cell-based therapy for pulmonary arterial hypertension. Cell Transplant, 2013, 22(8): 1325-1336.
11.	Chen H, Strappe P, Chen S, et al. Endothelial progenitor cells and pulmonary arterial hypertension. Heart Lung Circ, 2014, 23(7): 595-601.
12.	Xu W, Erzurum S C. Endothelial cell energy metabolism, prolifera-tion, and apoptosis in pulmonary hypertension. Compr Physiol, 2011, 1(1): 357-372.
13.	Farkas L, Kolb M. Vascular repair and regeneration as a therapeutic target for pulmonary arterial hypertension. Respiration, 2013, 85(5): 355-364.
14.	Baker CD, Seedorf GJ, Wishiewski BL, et al. Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol, 2013, 305(1): L73-L81.
15.	Mirsky R, Jahn S, Koskenvuo JW, et al. Treatment of pulmonary arterial hypertension with circulating angiogenic cells. Am J Physiol Lung Cell Mol Physiol, 2011, 301(1): L12-L19.
16.	Koutroumpi M, Dimopoulos S, Psarra K, et al. Circulating endothe-lial and progenitor cells: Evidence from acute and long-term exercise effects. World J Cardiol, 2012, 4(12): 312-326.
17.	Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997, 275(5302): 964-967.
18.	Yip HK, Chang LT, Sun CK, et al. Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats. Crit Care Med, 2008, 36(3): 873-880.
19.	Takahashi M, Nakamura T, Toba T, et al. Transplantation of endo-thelial progenitor cells into the lung to alleviate pulmonary hyper-tension in dogs. Tissue Eng, 2004, 10(5-6): 771-779.
20.	Marsboom G, Pokreisz P, Gheysens O, et al. Sustained endothelial progenitor cell dysfunction after chronic hypoxia-induced pulmo-nary hypertension. Stem Cells, 2008, 26(4): 1017-1026.
21.	赵科研, 王辉山, 侯明晓,等. 不同数目骨髓间充质干细胞移植对大鼠肺动脉高压的作用及内皮素-1表达的影响. 中国胸心血管外科临床杂志, 2012, 19(3): 298-303.
22.	Jungebluth P, Luedde M, Ferrer E, et al. Mesenchymal stem cells restore lung function by recruiting resident and nonresident proteins. Cell Transplant, 2011, 20(10): 1561-1574.
23.	Liang OD, Mitsialis SA, Chang MS, et al. Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells, 2011, 29(1): 99-107.
24.	Zhang Z H, Lu Y, Luan Y, et al. Effect of bone marrow mesenchymal stem cells on experimental pulmonary arterial hypertension. Exp Ther Med, 2012, 4(5): 839-843.
25.	Tian HJ, Yang JP, Wang XX. The effect of bone marrow mesench-ymal stem cell transplantation on hypoxic pulmonary hypertension in rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi, 2014, 30(3): 233-236.
26.	Jiang L, Song X H, Liu P, et al. Platelet-mediated mesenchymal stem cells homing to the lung reduces monocrotaline-induced rat pulmonary hypertension. Cell Transplant, 2012, 21(7): 1463-1475.
27.	Baber SR, Deng W, Master RG, et al. Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Heart Circ Physiol, 2007, 292(2): H1120-H1128.
28.	Luan Y, Zhang X, Kong F, et al. Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hyperten-sion through a paracrine mechanism. Int Immunopharmacol, 2012, 14(4): 432-437.
29.	Sacai R, Pullamsetti SS, Kolbe J, et al. Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med, 2012, 186(9): 897-908.
30.	Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther, 2010, 21(12): 1641-1655.
31.	Nemeth K, Keane-Myers A, Brown JM, et al. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci USA, 2010, 107(12): 5652-5657.
32.	Meisel R, Brpckers S, Heseler K, et al. Human but not murine multi-potent mesenchymal stromal cells exhibit broad-spectrum antimi-crobial effector function mediated by indoleamine 2, 3-dioxygenase. Leukemia, 2011, 25(4): 648-654.
33.	Ortiz LA, Dutreil M, Fattman C, et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA, 2007, 104(26): 11002-11007.
34.	Nemeth K, Leelahavanichkul A, Yuen PS, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogra-mming of host macrophages to increase their interleukin-10 production. Nat Med, 2009, 15(1): 42-49.
35.	Zhang Y, Liao S, Yang M, et al. Improved cell survival and paracrine capacity of human embryonic stem cell-derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension. Cell Transplant, 2012, 21(10): 2225-2239.
36.	Yen CH, Tsai TH, Leu S, et al. Sildenafil improves long-term effect of endothelial progenitor cell-based treatment for monocrotaline-induced rat pulmonary arterial hypertension. Cytotherapy, 2013, 15(2): 209-223.
37.	Sun CK, Lin YC, Yuen CM, et al. Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats. Int J Cardiol, 2012, 162(1): 45-58.
38.	Smadja DM, Mauge L, Gaussem P, et al. Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension. Angiogenesis, 2011, 14(1): 17-27.
39.	Kanki-Horimoto S, Horimoto H, Mieno S, et al. Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation, 2006, 114(1 Suppl): I181-I185.
40.	Takemiya K, Kai H, Yasukawa H, et al. Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats. Basic Res Cardiol, 2010, 105(3): 409-417.
41.	Shang F, He ZX, Wang HW, et al. Transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor gene for the treatment of pulmonary hypertension in rats. Zhonghua Yi Xue Za Zhi, 2011, 91(26): 1847-1851.

1. Kovacs G, Berghold A, Scheidl S, et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J, 2009, 34(4): 888-894.
2. Shimoda LA, Laurie SS. Vascular remodeling in pulmonary hyper-tension. J Mol Med (Berl), 2013, 91(3): 297-309.
3. Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol, 2009, 54(1 Suppl): S55-S66.
4. Pullamsetti SS, Schermuly R, Ghofrani A, et al. Novel and emerging therapies for pulmonary hypertension. Am J Respir Crit Care Med, 2014, 189(4): 394-400.
5. Aschermann M, Jansa P. Drug therapy of pulmonary arterial hypertension in 2014. Vnitr Lek, 2014, 60(4): 282-288.
6. 张清友, 杜军保. 肺动脉高压的治疗现状与进展. 临床儿科杂志, 2010, 28(7): 607-610.
7. Majka S, Burnham E, Stenmark KR. Cell-based therapies in pulmo-nary hypertension: who, what, and when? Am J Physiol Lung Cell Mol Physiol, 2011, 301(1): L9-L11.
8. Foster WS, Suen CM, Stewart DJ. Regenerative cell and tissue-based therapies for pulmonary arterial hypertension. Can J Cardiol, 2014, 30(11): 1350-1360.
9. Angelini A, Castellani C, Ravara B, et al. Stem-cell therapy in an experimental model of pulmonary hypertension and right heart failure: role of paracrine and neurohormonal milieu in the remode-ling process. J Heart Lung Transplant, 2011, 30(11): 1281-1293.
10. Yang JX, Pan YY, Zhao YY, et al. Endothelial progenitor cell-based therapy for pulmonary arterial hypertension. Cell Transplant, 2013, 22(8): 1325-1336.
11. Chen H, Strappe P, Chen S, et al. Endothelial progenitor cells and pulmonary arterial hypertension. Heart Lung Circ, 2014, 23(7): 595-601.
12. Xu W, Erzurum S C. Endothelial cell energy metabolism, prolifera-tion, and apoptosis in pulmonary hypertension. Compr Physiol, 2011, 1(1): 357-372.
13. Farkas L, Kolb M. Vascular repair and regeneration as a therapeutic target for pulmonary arterial hypertension. Respiration, 2013, 85(5): 355-364.
14. Baker CD, Seedorf GJ, Wishiewski BL, et al. Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol, 2013, 305(1): L73-L81.
15. Mirsky R, Jahn S, Koskenvuo JW, et al. Treatment of pulmonary arterial hypertension with circulating angiogenic cells. Am J Physiol Lung Cell Mol Physiol, 2011, 301(1): L12-L19.
16. Koutroumpi M, Dimopoulos S, Psarra K, et al. Circulating endothe-lial and progenitor cells: Evidence from acute and long-term exercise effects. World J Cardiol, 2012, 4(12): 312-326.
17. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997, 275(5302): 964-967.
18. Yip HK, Chang LT, Sun CK, et al. Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats. Crit Care Med, 2008, 36(3): 873-880.
19. Takahashi M, Nakamura T, Toba T, et al. Transplantation of endo-thelial progenitor cells into the lung to alleviate pulmonary hyper-tension in dogs. Tissue Eng, 2004, 10(5-6): 771-779.
20. Marsboom G, Pokreisz P, Gheysens O, et al. Sustained endothelial progenitor cell dysfunction after chronic hypoxia-induced pulmo-nary hypertension. Stem Cells, 2008, 26(4): 1017-1026.
21. 赵科研, 王辉山, 侯明晓,等. 不同数目骨髓间充质干细胞移植对大鼠肺动脉高压的作用及内皮素-1表达的影响. 中国胸心血管外科临床杂志, 2012, 19(3): 298-303.
22. Jungebluth P, Luedde M, Ferrer E, et al. Mesenchymal stem cells restore lung function by recruiting resident and nonresident proteins. Cell Transplant, 2011, 20(10): 1561-1574.
23. Liang OD, Mitsialis SA, Chang MS, et al. Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells, 2011, 29(1): 99-107.
24. Zhang Z H, Lu Y, Luan Y, et al. Effect of bone marrow mesenchymal stem cells on experimental pulmonary arterial hypertension. Exp Ther Med, 2012, 4(5): 839-843.
25. Tian HJ, Yang JP, Wang XX. The effect of bone marrow mesench-ymal stem cell transplantation on hypoxic pulmonary hypertension in rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi, 2014, 30(3): 233-236.
26. Jiang L, Song X H, Liu P, et al. Platelet-mediated mesenchymal stem cells homing to the lung reduces monocrotaline-induced rat pulmonary hypertension. Cell Transplant, 2012, 21(7): 1463-1475.
27. Baber SR, Deng W, Master RG, et al. Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Heart Circ Physiol, 2007, 292(2): H1120-H1128.
28. Luan Y, Zhang X, Kong F, et al. Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hyperten-sion through a paracrine mechanism. Int Immunopharmacol, 2012, 14(4): 432-437.
29. Sacai R, Pullamsetti SS, Kolbe J, et al. Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med, 2012, 186(9): 897-908.
30. Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther, 2010, 21(12): 1641-1655.
31. Nemeth K, Keane-Myers A, Brown JM, et al. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci USA, 2010, 107(12): 5652-5657.
32. Meisel R, Brpckers S, Heseler K, et al. Human but not murine multi-potent mesenchymal stromal cells exhibit broad-spectrum antimi-crobial effector function mediated by indoleamine 2, 3-dioxygenase. Leukemia, 2011, 25(4): 648-654.
33. Ortiz LA, Dutreil M, Fattman C, et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA, 2007, 104(26): 11002-11007.
34. Nemeth K, Leelahavanichkul A, Yuen PS, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogra-mming of host macrophages to increase their interleukin-10 production. Nat Med, 2009, 15(1): 42-49.
35. Zhang Y, Liao S, Yang M, et al. Improved cell survival and paracrine capacity of human embryonic stem cell-derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension. Cell Transplant, 2012, 21(10): 2225-2239.
36. Yen CH, Tsai TH, Leu S, et al. Sildenafil improves long-term effect of endothelial progenitor cell-based treatment for monocrotaline-induced rat pulmonary arterial hypertension. Cytotherapy, 2013, 15(2): 209-223.
37. Sun CK, Lin YC, Yuen CM, et al. Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats. Int J Cardiol, 2012, 162(1): 45-58.
38. Smadja DM, Mauge L, Gaussem P, et al. Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension. Angiogenesis, 2011, 14(1): 17-27.
39. Kanki-Horimoto S, Horimoto H, Mieno S, et al. Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation, 2006, 114(1 Suppl): I181-I185.
40. Takemiya K, Kai H, Yasukawa H, et al. Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats. Basic Res Cardiol, 2010, 105(3): 409-417.
41. Shang F, He ZX, Wang HW, et al. Transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor gene for the treatment of pulmonary hypertension in rats. Zhonghua Yi Xue Za Zhi, 2011, 91(26): 1847-1851.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Progress of Stem Cell Treatment of Pulmonary Arterial Hypertension

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