Use of mesenchymal stem cells for therapy of cardiac disease

Circulation Research

Volumn 116, Issue 8, 2015, Pages 1413-1430

  Karantalis, Vasileios ^a   Hare, Joshua M ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Cell differentiation; Mesenchymal stem cell; Regeneration; Stem cells

Indexed keywords

ADULT STEM CELL; ALLOGENEIC STEM CELL TRANSPLANTATION; ANGIOGENESIS; AUTOLOGOUS STEM CELL TRANSPLANTATION; CARDIOVASCULAR DISEASE; CELL DIFFERENTIATION; CELL PROLIFERATION; HEART DISEASE; HEART PROTECTION; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MESODERM; NONHUMAN; PRIORITY JOURNAL; REVIEW; STEM CELL EXPANSION; STEM CELL NICHE; TISSUE REGENERATION; ADVERSE EFFECTS; ANIMAL; CELL LINEAGE; CONVALESCENCE; HEART DISEASES; HEART MUSCLE; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PROCEDURES; REGENERATION; REGENERATIVE MEDICINE; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

BIOLOGICAL MARKER;

ANIMALS; BIOMARKERS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; HEART DISEASES; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MYOCARDIUM; PHENOTYPE; RECOVERY OF FUNCTION; REGENERATION; REGENERATIVE MEDICINE; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84936979255     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.116.303614     Document Type: Review

References (177)

1. Mozaffarian D, Benjamin EJ, Go AS, Heart disease and stroke statistics-2015 update: A report from the American Heart Association. Circulation 2015 131 e29 e322
2. McMurray JJ, Pfeffer MA., Heart failure. Lancet 2005; 365: 1877-1889. doi: 10.1016/S0140-6736(05)66621-4
3. Karantalis V, Balkan W, Schulman IH, Hatzistergos KE, Hare JM., Cell-based therapy for prevention and reversal of myocardial remodeling. Am J Physiol Heart Circ Physiol 2012 303 H256 H270. doi: 10.1152/ajpheart.00221.2012
4. Usunier B, Benderitter M, Tamarat R, Chapel A., Management of fibrosis: the mesenchymal stromal cells breakthrough. Stem Cells Int 2014 2014 340257. doi: 10.1155/2014/340257
5. Hare JM, Fishman JE, Gerstenblith G, Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 2012; 308: 2369-2379. doi: 10.1001/jama.2012.25321
6. Friedenstein AJ, Chailakhjan RK, Lalykina KS., The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3: 393-403.
7. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV., Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974; 17: 331-340.
8. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E., Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317. doi: 10.1080/14653240600855905
9. Deleted in proof.
10. Peister A, Mellad JA, Larson BL, Hall BM, Gibson LF, Prockop DJ., Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood 2004; 103: 1662-1668. doi: 10.1182/blood-2003-09-3070
11. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR., Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
12. Cao Y, Gomes SA, Rangel E, Paulino EC, Fonseca TL, Li J, Teixeira MB, Gouveia CH, Bianco AC, Kapiloff MS, Balkan W, Hare JM., S-nitrosoglutathione reductase-dependent PPARγ denitrosylation participates in adipogenesis and osteogenesis [published online ahead of print March 23, 2015]. J Clin Invest. doi: 10.1172/JCI73780. http://www.jci.org/articles/view/73780
13. Hass R, Kasper C, Böhm S, Jacobs R., Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 2011 9 12. doi: 10.1186/1478-811X-9-12
14. Pelekanos RA, Li J, Gongora M, Chandrakanthan V, Scown J, Suhaimi N, Brooke G, Christensen ME, Doan T, Rice AM, Osborne GW, Grimmond SM, Harvey RP, Atkinson K, Little MH., Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC-like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities. Stem Cell Res 2012; 8: 58-73. doi: 10.1016/j.scr.2011.08.003
15. Chong JJ, Chandrakanthan V, Xaymardan M, Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell 2011; 9: 527-540. doi: 10.1016/j.stem.2011.10.002
16. Yamada Y, Yokoyama S, Fukuda N, Kidoya H, Huang XY, Naitoh H, Satoh N, Takakura N., A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue. Biochem Biophys Res Commun 2007; 353: 182-188. doi: 10.1016/j.bbrc.2006.12.017
17. Breymann C, Schmidt D, Hoerstrup SP., Umbilical cord cells as a source of cardiovascular tissue engineering. Stem Cell Rev 2006; 2: 87-92. doi: 10.1007/s12015-006-0014-y
18. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, Maini RN., Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2000; 2: 477-488. doi: 10.1186/ar130
19. In 't Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE, Kanhai HH., Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003; 102: 1548-1549.
20. Perin L, Sedrakyan S, Da Sacco S, De Filippo R., Characterization of human amniotic fluid stem cells and their pluripotential capability. Methods Cell Biol 2008; 86: 85-99. doi: 10.1016/S0091-679X(08)00005-8
21. De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A., Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007; 25: 100-106. doi: 10.1038/nbt1274
22. Roubelakis MG, Pappa KI, Bitsika V, Zagoura D, Vlahou A, Papadaki HA, Antsaklis A, Anagnou NP., Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev 2007; 16: 931-952. doi: 10.1089/scd.2007.0036
23. Tsai MS, Lee JL, Chang YJ, Hwang SM., Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod 2004; 19: 1450-1456. doi: 10.1093/humrep/deh279
24. Simmons PJ, Torok-Storb B., Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 1991; 78: 55-62.
25. Battula VL, Treml S, Bareiss PM, Gieseke F, Roelofs H, de Zwart P, Müller I, Schewe B, Skutella T, Fibbe WE, Kanz L, Bühring HJ., Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1. Haematologica 2009; 94: 173-184. doi: 10.3324/haematol.13740
26. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marbán L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marbán E., Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 2012; 379: 895-904. doi: 10.1016/S0140-6736(12)60195-0
27. Vecellio M, Meraviglia V, Nanni S, Barbuti A, Scavone A, DiFrancesco D, Farsetti A, Pompilio G, Colombo GI, Capogrossi MC, Gaetano C, Rossini A., In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors. PLoS One 2012 7 e51694. doi: 10.1371/journal.pone.0051694
28. Rossini A, Frati C, Lagrasta C, Human cardiac and bone marrow stromal cells exhibit distinctive properties related to their origin. Cardiovasc Res 2011; 89: 650-660. doi: 10.1093/cvr/cvq290
29. Meraviglia V, Azzimato V, Piacentini L, Chiesa M, Kesharwani RK, Frati C, Capogrossi MC, Gaetano C, Pompilio G, Colombo GI, Rossini A., Syngeneic cardiac and bone marrow stromal cells display tissue-specific microRNA signatures and microRNA subsets restricted to diverse differentiation processes. PLoS One 2014 9 e107269. doi: 10.1371/journal.pone.0107269
30. Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM., Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 2002; 30: 896-904.
31. Sohni A, Verfaillie CM., Multipotent adult progenitor cells. Best Pract Res Clin Haematol 2011; 24: 3-11. doi: 10.1016/j.beha.2011.01.006
32. Choi YH, Kurtz A, Stamm C., Mesenchymal stem cells for cardiac cell therapy. Hum Gene Ther 2011; 22: 3-17. doi: 10.1089/hum.2010.211
33. Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J., Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev 2012; 21: 2724-2752. doi: 10.1089/scd.2011.0722
34. Lennon DP, Caplan AI., Isolation of human marrow-derived mesenchymal stem cells. Exp Hematol 2006; 34: 1604-1605. doi: 10.1016/j.exphem.2006.07.014
35. Liu Y, Berendsen AD, Jia S, Lotinun S, Baron R, Ferrara N, Olsen BR., Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation. J Clin Invest 2012; 122: 3101-3113. doi: 10.1172/JCI61209
36. Liu Y, Song J, Liu W, Wan Y, Chen X, Hu C., Growth and differentiation of rat bone marrow stromal cells: does 5-azacytidine trigger their cardiomyogenic differentiation? Cardiovasc Res 2003; 58: 460-468.
37. Shim WS, Jiang S, Wong P, Tan J, Chua YL, Tan YS, Sin YK, Lim CH, Chua T, Teh M, Liu TC, Sim E., Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells. Biochem Biophys Res Commun 2004; 324: 481-488. doi: 10.1016/j.bbrc.2004.09.087
38. Yoon J, Min BG, Kim YH, Shim WJ, Ro YM, Lim DS., Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. Acta Cardiol 2005; 60: 277-284.
39. Pereira RF, Halford KW, O'Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ., Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A 1995; 92: 4857-4861.
40. Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF., Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng 1998; 4: 415-428.
41. Woodbury D, Schwarz EJ, Prockop DJ, Black IB., Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61: 364-370.
42. Li X, Yu X, Lin Q, Deng C, Shan Z, Yang M, Lin S., Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment. J Mol Cell Cardiol 2007; 42: 295-303. doi: 10.1016/j.yjmcc.2006.07.002
43. Pijnappels DA, Schalij MJ, Ramkisoensing AA, van Tuyn J, de Vries AA, van der Laarse A, Ypey DL, Atsma DE., Forced alignment of mesenchymal stem cells undergoing cardiomyogenic differentiation affects functional integration with cardiomyocyte cultures. Circ Res 2008; 103: 167-176. doi: 10.1161/CIRCRESAHA.108.176131
44. Xu M, Wani M, Dai YS, Wang J, Yan M, Ayub A, Ashraf M., Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes. Circulation 2004; 110: 2658-2665. doi: 10.1161/01.CIR.0000145609.20435.36
45. Cook D, Genever P., Regulation of mesenchymal stem cell differentiation. Adv Exp Med Biol 2013; 786: 213-229. doi: 10.1007/978-94-007-6621-1-12
46. Westendorf JJ, Kahler RA, Schroeder TM., Wnt signaling in osteoblasts and bone diseases. Gene 2004; 341: 19-39. doi: 10.1016/j.gene.2004.06.044
47. van den Akker F, de Jager SC, Sluijter JP., Mesenchymal stem cell therapy for cardiac inflammation: immunomodulatory properties and the influence of toll-like receptors. Mediators Inflamm 2013 2013 181020. doi: 10.1155/2013/181020
48. Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L, Le Blanc K., Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006; 81: 1390-1397. doi: 10.1097/01.tp.0000214462.63943.14
49. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99: 3838-3843.
50. Mándi Y, Vécsei L., The kynurenine system and immunoregulation. J Neural Transm 2012; 119: 197-209. doi: 10.1007/s00702-011-0681-y
51. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ., Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009; 5: 54-63. doi: 10.1016/j.stem.2009.05.003
52. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L., Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008; 111: 1327-1333. doi: 10.1182/blood-2007-02-074997
53. Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC., Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 2004; 13: 263-271. doi: 10.1089/154732804323099190
54. Lambert JM, Lopez EF, Lindsey ML., Macrophage roles following myocardial infarction. Int J Cardiol 2008; 130: 147-158. doi: 10.1016/j.ijcard.2008.04.059
55. Barin JG, Rose NR, Ciháková D., Macrophage diversity in cardiac inflammation: a review. Immunobiology 2012; 217: 468-475. doi: 10.1016/j.imbio.2011.06.009
56. Maggini J, Mirkin G, Bognanni I, Holmberg J, Piazzón IM, Nepomnaschy I, Costa H, Cañones C, Raiden S, Vermeulen M, Geffner JR., Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One 2010 5 e9252. doi: 10.1371/journal.pone.0009252
57. Frangogiannis NG., Regulation of the inflammatory response in cardiac repair. Circ Res 2012; 110: 159-173. doi: 10.1161/CIRCRESAHA.111.243162
58. Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA, McIntosh KR, Mosca JD., Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003; 10: 228-241. doi: 68710
59. Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, Li RK., Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation 2010; 122: 2419-2429. doi: 10.1161/CIRCULATIONAHA.110.955971
60. English K, Mahon BP., Allogeneic mesenchymal stem cells: agents of immune modulation. J Cell Biochem 2011; 112: 1963-1968. doi: 10.1002/jcb.23119
61. Ascheim DD, Gelijns AC, Goldstein D, Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation 2014; 129: 2287-2296. doi: 10.1161/CIRCULATIONAHA.113.007412
62. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ., Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005; 11: 367-368. doi: 10.1038/nm0405-367
63. Herrmann JL, Wang Y, Abarbanell AM, Weil BR, Tan J, Meldrum DR., Preconditioning mesenchymal stem cells with transforming growth factor-alpha improves mesenchymal stem cell-mediated cardioprotection. Shock 2010; 33: 24-30. doi: 10.1097/SHK.0b013e3181b7d137
64. Schuleri KH, Feigenbaum GS, Centola M, Weiss ES, Zimmet JM, Turney J, Kellner J, Zviman MM, Hatzistergos KE, Detrick B, Conte JV, McNiece I, Steenbergen C, Lardo AC, Hare JM., Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J 2009; 30: 2722-2732. doi: 10.1093/eurheartj/ehp265
65. Hatzistergos KE, Quevedo H, Oskouei BN, Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res 2010; 107: 913-922. doi: 10.1161/CIRCRESAHA.110.222703
66. Amado LC, Saliaris AP, Schuleri KH, St John M, Xie JS, Cattaneo S, Durand DJ, Fitton T, Kuang JQ, Stewart G, Lehrke S, Baumgartner WW, Martin BJ, Heldman AW, Hare JM., Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 2005; 102: 11474-11479. doi: 10.1073/pnas.0504388102
67. Amado LC, Schuleri KH, Saliaris AP, Boyle AJ, Helm R, Oskouei B, Centola M, Eneboe V, Young R, Lima JA, Lardo AC, Heldman AW, Hare JM., Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol 2006; 48: 2116-2124. doi: 10.1016/j.jacc.2006.06.073
68. Karantalis V, DiFede DL, Gerstenblith G, Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ Res 2014; 114: 1302-1310. doi: 10.1161/CIRCRESAHA.114.303180
69. Heldman AW, DiFede DL, Fishman JE, Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA 2014; 311: 62-73. doi: 10.1001/jama.2013.282909
70. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, Denktas AE, Gammon RS, Hermiller JB Jr, Reisman MA, Schaer GL, Sherman W., A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 2009; 54: 2277-2286. doi: 10.1016/j.jacc.2009.06.055
71. Molina EJ, Palma J, Gupta D, Torres D, Gaughan JP, Houser S, Macha M., Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy. J Tissue Eng Regen Med 2009; 3: 85-91. doi: 10.1002/term.137
72. Psaltis PJ, Zannettino AC, Worthley SG, Gronthos S., Concise review: mesenchymal stromal cells: potential for cardiovascular repair. Stem Cells 2008; 26: 2201-2210. doi: 10.1634/stemcells.2008-0428
73. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD., Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002; 105: 93-98.
74. Müller-Ehmsen J, Krausgrill B, Burst V, Schenk K, Neisen UC, Fries JW, Fleischmann BK, Hescheler J, Schwinger RH., Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction. J Mol Cell Cardiol 2006; 41: 876-884. doi: 10.1016/j.yjmcc.2006.07.023
75. Quevedo HC, Hatzistergos KE, Oskouei BN, Feigenbaum GS, Rodriguez JE, Valdes D, Pattany PM, Zambrano JP, Hu Q, McNiece I, Heldman AW, Hare JM., Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci U S A 2009; 106: 14022-14027. doi: 10.1073/pnas.0903201106
76. Silva GV, Litovsky S, Assad JA, Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 2005; 111: 150-156. doi: 10.1161/01.CIR.0000151812.86142.45
77. Lim SY, Kim YS, Ahn Y, Jeong MH, Hong MH, Joo SY, Nam KI, Cho JG, Kang PM, Park JC., The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovasc Res 2006; 70: 530-542. doi: 10.1016/j.cardiores.2006.02.016
78. Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V., Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A 2007; 104: 1643-1648. doi: 10.1073/pnas.0610024104
79. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL., Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 2004; 109: 1292-1298. doi: 10.1161/01.CIR.0000121425.42966.F1
80. Rogers TB, Pati S, Gaa S, Riley D, Khakoo AY, Patel S, Wardlow RD II, Frederick CA, Hall G, He LP, Lederer WJ., Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes. J Mol Cell Cardiol 2011; 50: 346-356. doi: 10.1016/j.yjmcc.2010.09.001
81. Li W, Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, Furlani D, Piechaczek C, Moebius JM, Lützow K, Lendlein A, Stamm C, Li RK, Steinhoff G., Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 2007; 25: 2118-2127. doi: 10.1634/stemcells.2006-0771
82. Asahara T, Kawamoto A, Masuda H., Concise review: Circulating endothelial progenitor cells for vascular medicine. Stem Cells 2011; 29: 1650-1655. doi: 10.1002/stem.745
83. Williams AR, Hare JM., Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 2011; 109: 923-940. doi: 10.1161/CIRCRESAHA.111.243147
84. Premer C, Blum A, Bellio M, Schulman IH, Sierra J, Hurwitz B, Parker M, Demarkarian C, DiFede D, Balkan W, Khan A, Hare JM., Allogeneic mesenchymal stem cells restore endothelial function in heart failure by stimulating endothelial progenitor cells. E-Biomedicine 2015 In press
85. Cai X, Lin Y, Friedrich CC, Neville C, Pomerantseva I, Sundback CA, Sharma P, Zhang Z, Vacanti JP, Hauschka PV, Grottkau BE., Bone marrow derived pluripotent cells are pericytes which contribute to vascularization. Stem Cell Rev 2009; 5: 437-445. doi: 10.1007/s12015-009-9097-6
86. Crisan M, Yap S, Casteilla L, A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008; 3: 301-313. doi: 10.1016/j.stem.2008.07.003
87. Davani S, Marandin A, Mersin N, Royer B, Kantelip B, Herve P, Etievent JP, Kantelip JP., Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation 2003; 108 (Suppl 1) II253-II258.
88. Gomes SA, Rangel EB, Premer C, Dulce RA, Cao Y, Florea V, Balkan W, Rodrigues CO, Schally AV, Hare JM., S-nitrosoglutathione reductase (GSNOR) enhances vasculogenesis by mesenchymal stem cells. Proc Natl Acad Sci U S A 2013; 110: 2834-2839. doi: 10.1073/pnas.1220185110
89. Markel TA, Wang Y, Herrmann JL, Crisostomo PR, Wang M, Novotny NM, Herring CM, Tan J, Lahm T, Meldrum DR., VEGF is critical for stem cell-mediated cardioprotection and a crucial paracrine factor for defining the age threshold in adult and neonatal stem cell function. Am J Physiol Heart Circ Physiol 2008 295 H2308 H2314. doi: 10.1152/ajpheart.00565.2008
90. De Lisio M, Jensen T, Sukiennik RA, Huntsman HD, Boppart MD., Substrate and strain alter the muscle-derived mesenchymal stem cell secretome to promote myogenesis. Stem Cell Res Ther 2014 5 74. doi: 10.1186/scrt463
91. Chen X, Li Y., Role of matrix metalloproteinases in skeletal muscle: migration, differentiation, regeneration and fibrosis. Cell Adh Migr 2009; 3: 337-341.
92. Serrano AL, Mann CJ, Vidal B, Ardite E, Perdiguero E, Muñoz-Cánoves P., Cellular and molecular mechanisms regulating fibrosis in skeletal muscle repair and disease. Curr Top Dev Biol 2011; 96: 167-201. doi: 10.1016/B978-0-12-385940-2.00007-3
93. Willems E, Cabral-Teixeira J, Schade D, Cai W, Reeves P, Bushway PJ, Lanier M, Walsh C, Kirchhausen T, Izpisua Belmonte JC, Cashman J, Mercola M., Small molecule-mediated TGF-β type II receptor degradation promotes cardiomyogenesis in embryonic stem cells. Cell Stem Cell 2012; 11: 242-252. doi: 10.1016/j.stem.2012.04.025
94. Tan G, Shim W, Gu Y, Qian L, Chung YY, Lim SY, Yong P, Sim E, Wong P., Differential effect of myocardial matrix and integrins on cardiac differentiation of human mesenchymal stem cells. Differentiation 2010; 79: 260-271. doi: 10.1016/j.diff.2010.02.005
95. Tang J, Wang J, Guo L, Kong X, Yang J, Zheng F, Zhang L, Huang Y., Mesenchymal stem cells modified with stromal cell-derived factor 1 alpha improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Mol Cells 2010; 29: 9-19. doi: 10.1007/s10059-010-0001-7
96. Shu T, Zeng B, Ren X, Li Y., HO-1 modified mesenchymal stem cells modulate MMPs/TIMPs system and adverse remodeling in infarcted myocardium. Tissue Cell 2010; 42: 217-222. doi: 10.1016/j.tice.2010.04.004
97. Mias C, Lairez O, Trouche E, Roncalli J, Calise D, Seguelas MH, Ordener C, Piercecchi-Marti MD, Auge N, Salvayre AN, Bourin P, Parini A, Cussac D., Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction. Stem Cells 2009; 27: 2734-2743. doi: 10.1002/stem.169
98. Loffredo FS, Steinhauser ML, Gannon J, Lee RT., Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 2011; 8: 389-398. doi: 10.1016/j.stem.2011.02.002
99. Suzuki G, Iyer V, Lee TC, Canty JM Jr, Autologous mesenchymal stem cells mobilize cKit+ and CD133+ bone marrow progenitor cells and improve regional function in hibernating myocardium. Circ Res 2011; 109: 1044-1054. doi: 10.1161/CIRCRESAHA.111.245969
100. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P., Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-776.
101. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A., Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 2003; 425: 968-973. doi: 10.1038/nature02069
102. Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, Morales AR, Da Silva J, Sussman MA, Heldman AW, Hare JM., Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation 2013; 127: 213-223. doi: 10.1161/CIRCULATIONAHA.112.131110
103. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González MÁ Bernad A, Sánchez-Madrid F., Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2011 2 282. doi: 10.1038/ncomms1285
104. Gusachenko ON, Zenkova MA, Vlassov VV., Nucleic acids in exosomes: disease markers and intercellular communication molecules. Biochemistry (Mosc) 2013; 78: 1-7. doi: 10.1134/S000629791301001X
105. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654-659. doi: 10.1038/ncb1596
106. Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM., Exosomes: Fit to deliver small RNA. Commun Integr Biol 2010; 3: 447-450. doi: 10.4161/cib.3.5.12339
107. Théry C, Zitvogel L, Amigorena S., Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2: 569-579. doi: 10.1038/nri855
108. Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ., Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 2005; 113: 752-760. doi: 10.1002/ijc.20657
109. Verweij FJ, van Eijndhoven MA, Middeldorp J, Pegtel DM., Analysis of viral microRNA exchange via exosomes in vitro and in vivo. Methods Mol Biol 2013; 1024: 53-68. doi: 10.1007/978-1-62703-453-1-5
110. Herrera MB, Fonsato V, Gatti S, Deregibus MC, Sordi A, Cantarella D, Calogero R, Bussolati B, Tetta C, Camussi G., Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med 2010; 14: 1605-1618. doi: 10.1111/j.1582-4934.2009.00860.x
111. Deregibus MC, Cantaluppi V, Calogero R, Lo Iacono M, Tetta C, Biancone L, Bruno S, Bussolati B, Camussi G., Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007; 110: 2440-2448. doi: 10.1182/blood-2007-03-078709
112. Yuan A, Farber EL, Rapoport AL, Tejada D, Deniskin R, Akhmedov NB, Farber DB., Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One 2009 4 e4722. doi: 10.1371/journal.pone.0004722
113. Camussi G, Deregibus MC, Bruno S, Grange C, Fonsato V, Tetta C., Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res 2011; 1: 98-110.
114. Katsuda T, Kosaka N, Takeshita F, Ochiya T., The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics 2013; 13: 1637-1653. doi: 10.1002/pmic.201200373
115. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 2010; 4: 214-222. doi: 10.1016/j.scr.2009.12.003
116. Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ, Lim SK., Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev 2013; 65: 336-341. doi: 10.1016/j.addr.2012.07.001
117. Reis LA, Borges FT, Simões MJ, Borges AA, Sinigaglia-Coimbra R, Schor N., Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats. PLoS One 2012 7 e44092. doi: 10.1371/journal.pone.0044092
118. Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, Shang X, Zhang ZG, Chopp M., Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 2012; 30: 1556-1564. doi: 10.1002/stem.1129
119. Spees JL, Olson SD, Whitney MJ, Prockop DJ., Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 2006; 103: 1283-1288. doi: 10.1073/pnas.0510511103
120. Lai RC, Tan SS, Teh BJ, Sze SK, Arslan F, de Kleijn DP, Choo A, Lim SK., Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome. Int J Proteomics 2012 2012 971907. doi: 10.1155/2012/971907
121. Pasquier J, Guerrouahen BS, Al Thawadi H, Ghiabi P, Maleki M, Abu-Kaoud N, Jacob A, Mirshahi M, Galas L, Rafii S, Le Foll F, Rafii A., Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance. J Transl Med 2013 11 94. doi: 10.1186/1479-5876-11-94
122. Ahmad T, Mukherjee S, Pattnaik B, Kumar M, Singh S, Kumar M, Rehman R, Tiwari BK, Jha KA, Barhanpurkar AP, Wani MR, Roy SS, Mabalirajan U, Ghosh B, Agrawal A., Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. EMBO J 2014; 33: 994-1010. doi: 10.1002/embj.201386030
123. Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harris S, Wiedemann LM, Mishina Y, Li L., Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003; 425: 836-841. doi: 10.1038/nature02041
124. Pasolli HA., The hair follicle bulge: a niche for adult stem cells. Microsc Microanal 2011; 17: 513-519. doi: 10.1017/S1431927611000419
125. Yeung TM, Chia LA, Kosinski CM, Kuo CJ., Regulation of self-renewal and differentiation by the intestinal stem cell niche. Cell Mol Life Sci 2011; 68: 2513-2523. doi: 10.1007/s00018-011-0687-5
126. Urbanek K, Cesselli D, Rota M, Nascimbene A, De Angelis A, Hosoda T, Bearzi C, Boni A, Bolli R, Kajstura J, Anversa P, Leri A., Stem cell niches in the adult mouse heart. Proc Natl Acad Sci U S A 2006; 103: 9226-9231. doi: 10.1073/pnas.0600635103
127. Mazhari R, Hare JM., Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat Clin Pract Cardiovasc Med 2007; 4 (Suppl 1) S21-S26. doi: 10.1038/ncpcardio0770
128. Shi M, Li J, Liao L, Chen B, Li B, Chen L, Jia H, Zhao RC., Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica 2007; 92: 897-904.
129. Engel FB, Hsieh PC, Lee RT, Keating MT., FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. Proc Natl Acad Sci U S A 2006; 103: 15546-15551. doi: 10.1073/pnas.0607382103
130. Yang YJ, Qian HY, Huang J, Li JJ, Gao RL, Dou KF, Yang GS, Willerson JT, Geng YJ., Combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells increases benefits in infarcted swine hearts. Arterioscler Thromb Vasc Biol 2009; 29: 2076-2082. doi: 10.1161/ATVBAHA.109.189662
131. Wisel S, Khan M, Kuppusamy ML, Mohan IK, Chacko SM, Rivera BK, Sun BC, Hideg K, Kuppusamy P., Pharmacological preconditioning of mesenchymal stem cells with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine) protects hypoxic cells against oxidative stress and enhances recovery of myocardial function in infarcted heart through Bcl-2 expression. J Pharmacol Exp Ther 2009; 329: 543-550. doi: 10.1124/jpet.109.150839
132. Guo J, Lin G, Bao C, Hu Z, Chu H, Hu M., Insulin-like growth factor 1 improves the efficacy of mesenchymal stem cells transplantation in a rat model of myocardial infarction. J Biomed Sci 2008; 15: 89-97. doi: 10.1007/s11373-007-9207-x
133. Pons J, Huang Y, Arakawa-Hoyt J, Washko D, Takagawa J, Ye J, Grossman W, Su H., VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochem Biophys Res Commun 2008; 376: 419-422. doi: 10.1016/j.bbrc.2008.09.003
134. Zeng B, Ren X, Lin G, Zhu C, Chen H, Yin J, Jiang H, Yang B, Ding D., Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement. Cell Biol Int 2008; 32: 1256-1264. doi: 10.1016/j.cellbi.2008.07.010
135. Hahn JY, Cho HJ, Kang HJ, Kim TS, Kim MH, Chung JH, Bae JW, Oh BH, Park YB, Kim HS., Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J Am Coll Cardiol 2008; 51: 933-943. doi: 10.1016/j.jacc.2007.11.040
136. Zhang M, Mal N, Kiedrowski M, Chacko M, Askari AT, Popovic ZB, Koc ON, Penn MS., SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J 2007; 21: 3197-3207. doi: 10.1096/fj.06-6558com
137. Qi CM, Ma GS, Liu NF, Shen CX, Chen Z, Liu XJ, Hu YP, Zhang XL, Teng GJ, Ju SH, Ma M, Tang YL., Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model. Chin Med J (Engl) 2008; 121: 544-550.
138. Hashemi SM, Ghods S, Kolodgie FD, Parcham-Azad K, Keane M, Hamamdzic D, Young R, Rippy MK, Virmani R, Litt H, Wilensky RL., A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction. Eur Heart J 2008; 29: 251-259. doi: 10.1093/eurheartj/ehm559
139. Hamamoto H, Gorman JH III, Ryan LP, Hinmon R, Martens TP, Schuster MD, Plappert T, Kiupel M, St John-Sutton MG, Itescu S, Gorman RC., Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. Ann Thorac Surg 2009; 87: 794-801. doi: 10.1016/j.athoracsur.2008.11.057
140. Houtgraaf JH, de Jong R, Kazemi K, de Groot D, van der Spoel TI, Arslan F, Hoefer I, Pasterkamp G, Itescu S, Zijlstra F, Geleijnse ML, Serruys PW, Duckers HJ., Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res 2013; 113: 153-166. doi: 10.1161/CIRCRESAHA.112.300730
141. Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, Pittenger MF, Martin BJ., Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 2002; 73: 1919-1925.; discussion 1926
142. Ohnishi S, Yanagawa B, Tanaka K, Miyahara Y, Obata H, Kataoka M, Kodama M, Ishibashi-Ueda H, Kangawa K, Kitamura S, Nagaya N., Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J Mol Cell Cardiol 2007; 42: 88-97. doi: 10.1016/j.yjmcc.2006.10.003
143. Plotnikov AN, Shlapakova I, Szabolcs MJ, Danilo P Jr, Lorell BH, Potapova IA, Lu Z, Rosen AB, Mathias RT, Brink PR, Robinson RB, Cohen IS, Rosen MR., Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 2007; 116: 706-713. doi: 10.1161/CIRCULATIONAHA.107.703231
144. Vincentelli A, Wautot F, Juthier F, Fouquet O, Corseaux D, Marechaux S, Le Tourneau T, Fabre O, Susen S, Van Belle E, Mouquet F, Decoene C, Prat A, Jude B., In vivo autologous recellularization of a tissue-engineered heart valve: are bone marrow mesenchymal stem cells the best candidates? J Thorac Cardiovasc Surg 2007; 134: 424-432. doi: 10.1016/j.jtcvs.2007.05.005
145. Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ, Canadian Critical Care Trials Group Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 2012 7 e47559. doi: 10.1371/journal.pone.0047559
146. Miura M, Miura Y, Padilla-Nash HM, Molinolo AA, Fu B, Patel V, Seo BM, Sonoyama W, Zheng JJ, Baker CC, Chen W, Ried T, Shi S., Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells 2006; 24: 1095-1103. doi: 10.1634/stemcells.2005-0403
147. Hare JM, Fishman JE, Gerstenblith G, Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 2012; 308: 2369-2379. doi: 10.1001/jama.2012.25321
148. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, Zhang JJ, Chunhua RZ, Liao LM, Lin S, Sun JP., Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 2004; 94: 92-95. doi: 10.1016/j.amjcard.2004.03.034
149. Houtgraaf JH, den Dekker WK, van Dalen BM, Springeling T, de Jong R, van Geuns RJ, Geleijnse ML, Fernandez-Aviles F, Zijlsta F, Serruys PW, Duckers HJ., First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2012; 59: 539-540. doi: 10.1016/j.jacc.2011.09.065
150. Perin EC, Sanz-Ruiz R, Sanchez PL, Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The precise trial. Am Heart J 2014; 168: 88-95.e82. doi: 10.1016/j.ahj.2014.03.022
151. Bartunek J, Behfar A, Dolatabadi D, Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol 2013; 61: 2329-2338. doi: 10.1016/j.jacc.2013.02.071
152. Suncion VY, Ghersin E, Fishman JE, Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial. Circ Res 2014; 114: 1292-1301. doi: 10.1161/CIRCRESAHA.114.302854
153. Qayyum AA, Haack-Sørensen M, Mathiasen AB, Jørgensen E, Ekblond A, Kastrup J., Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design. Regen Med 2012; 7: 421-428. doi: 10.2217/rme.12.17
154. Mushtaq M, DiFede DL, Golpanian S, Khan A, Gomes SA, Mendizabal A, Heldman AW, Hare JM., Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy. J Cardiovasc Transl Res 2014; 7: 769-780. doi: 10.1007/s12265-014-9594-0
155. Sethe S, Scutt A, Stolzing A., Aging of mesenchymal stem cells. Ageing Res Rev 2006; 5: 91-116. doi: 10.1016/j.arr.2005.10.001
156. Fan M, Chen W, Liu W, Du GQ, Jiang SL, Tian WC, Sun L, Li RK, Tian H., The effect of age on the efficacy of human mesenchymal stem cell transplantation after a myocardial infarction. Rejuvenation Res 2010; 13: 429-438. doi: 10.1089/rej.2009.0986
157. Zhang H, Fazel S, Tian H, Mickle DA, Weisel RD, Fujii T, Li RK., Increasing donor age adversely impacts beneficial effects of bone marrow but not smooth muscle myocardial cell therapy. Am J Physiol Heart Circ Physiol 2005 289 H2089 H2096. doi: 10.1152/ajpheart.00019.2005
158. Khan M, Mohsin S, Khan SN, Riazuddin S., Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice. J Cell Mol Med 2011; 15: 1515-1527. doi: 10.1111/j.1582-4934.2009.00998.x
159. Golpanian S, El-Khorazaty J, Mendizabal A, DiFede DL, Suncion VY, Karantalis V, Fishman JE, Ghersin E, Balkan W, Hare JM., Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients. J Am Coll Cardiol 2015; 65: 125-132. doi: 10.1016/j.jacc.2014.10.040
160. Crisostomo PR, Wang M, Herring CM, Markel TA, Meldrum KK, Lillemoe KD, Meldrum DR., Gender differences in injury induced mesenchymal stem cell apoptosis and VEGF, TNF, IL-6 expression: role of the 55 kDa TNF receptor (TNFR1). J Mol Cell Cardiol 2007; 42: 142-149. doi: 10.1016/j.yjmcc.2006.09.016
161. Chen HY, Zhang X, Chen SF, Zhang YX, Liu YH, Ma LL, Wang LX., The protective effect of 17β-estradiol against hydrogen peroxide-induced apoptosis on mesenchymal stem cell. Biomed Pharmacother 2012; 66: 57-63. doi: 10.1016/j.biopha.2011.11.014
162. Zhao ZG, Liang Y, Li K, Li WM, Li QB, Chen ZC, Zou P., Phenotypic and functional comparison of mesenchymal stem cells derived from the bone marrow of normal adults and patients with hematologic malignant diseases. Stem Cells Dev 2007; 16: 637-648. doi: 10.1089/scd.2007.0008
163. Kastrinaki MC, Sidiropoulos P, Roche S, Ringe J, Lehmann S, Kritikos H, Vlahava VM, Delorme B, Eliopoulos GD, Jorgensen C, Charbord P, Häupl T, Boumpas DT, Papadaki HA., Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis 2008; 67: 741-749. doi: 10.1136/ard.2007.076174
164. Yang Q, Chen C, Wu S, Zhang Y, Mao X, Wang W., Advanced glycation end products downregulates peroxisome proliferator-activated receptor γ expression in cultured rabbit chondrocyte through MAPK pathway. Eur J Pharmacol 2010; 649: 108-114. doi: 10.1016/j.ejphar.2010.09.025
165. Kim BS, Kim SJ, Kim HJ, Lee SJ, Park YJ, Lee J, You HK., Effects of nicotine on proliferation and osteoblast differentiation in human alveolar bone marrow-derived mesenchymal stem cells. Life Sci 2012; 90: 109-115. doi: 10.1016/j.lfs.2011.10.019
166. Selem SM, Kaushal S, Hare JM., Stem cell therapy for pediatric dilated cardiomyopathy. Curr Cardiol Rep 2013 15 369. doi: 10.1007/s11886-013-0369-z
167. Ishigami S, Ohtsuki S, Tarui S, Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP Prospective Phase 1 Controlled Trial. Circ Res 2015; 116: 653-664. doi: 10.1161/CIRCRESAHA.116.304671
168. Losordo DW, Henry TD, Davidson C, ACT34-CMI Investigators Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 2011; 109: 428-436. doi: 10.1161/CIRCRESAHA.111.245993
169. Quyyumi AA, Waller EK, Murrow J, CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J 2011; 161: 98-105. doi: 10.1016/j.ahj.2010.09.025
170. Mohammadi Gorji S, Karimpor Malekshah AA, Hashemi-Soteh MB, Rafiei A, Parivar K, Aghdami N., Effect of mesenchymal stem cells on Doxorubicin-induced fibrosis. Cell J 2012; 14: 142-151.
171. Kang SK, Shin IS, Ko MS, Jo JY, Ra JC., Journey of mesenchymal stem cells for homing: strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int 2012 2012 342968. doi: 10.1155/2012/342968
172. Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA, Leor J., Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003; 108: 863-868. doi: 10.1161/01.CIR.0000084828.50310.6A
173. Price MJ, Chou CC, Frantzen M, Miyamoto T, Kar S, Lee S, Shah PK, Martin BJ, Lill M, Forrester JS, Chen PS, Makkar RR., Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 2006; 111: 231-239. doi: 10.1016/j.ijcard.2005.07.036
174. Hou D, Youssef EA, Brinton TJ, Zhang P, Rogers P, Price ET, Yeung AC, Johnstone BH, Yock PG, March KL., Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005 112 I150 I156. doi: 10.1161/CIRCULATIONAHA.104.526749
175. Perin EC, Silva GV, Assad JA, Vela D, Buja LM, Sousa AL, Litovsky S, Lin J, Vaughn WK, Coulter S, Fernandes MR, Willerson JT., Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 2008; 44: 486-495. doi: 10.1016/j.yjmcc.2007.09.012
176. Traverse JH, Henry TD, Pepine CJ, Cardiovascular Cell Therapy Research Network (CCTRN) Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA 2012; 308: 2380-2389. doi: 10.1001/jama.2012.28726
177. Traverse JH, Henry TD, Vaughan DE, Cardiovascular Cell Therapy Research Network LateTIME: a phase-II, randomized, double-blinded, placebo-controlled, pilot trial evaluating the safety and effect of administration of bone marrow mononuclear cells 2 to 3 weeks after acute myocardial infarction. Tex Heart Inst J 2010; 37: 412-420.