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Review

Perspective and challenges of mesenchymal stem cells for cardiovascular regeneration

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Pages 505-517 | Published online: 10 Jan 2014

References

  • Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 28(2), 208–216 (2008).
  • Wang X, Zhao T, Huang W et al. Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells 27(12), 3021–3031 (2009).
  • Li H, Zuo S, He Z et al. Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival. Am. J. Physiol. Heart Circ. Physiol. 299(6), H1772–H1781 (2010).
  • Cho J, Zhai P, Maejima Y, Sadoshima J. Myocardial injection with GSK-3b-overexpressing bone marrow-derived mesenchymal stem cells attenuates cardiac dysfunction after myocardial infarction. Circ. Res. 108(4), 478–489 (2011).
  • Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361(9351), 47–49 (2003).
  • Kim SW, Zhang HZ, Kim CE, An HS, Kim JM, Kim MH. Amniotic mesenchymal stem cells have robust angiogenic properties and are effective in treating hindlimb ischaemia. Cardiovasc. Res. 93(3), 525–534 (2012).
  • Lian Q, Zhang Y, Zhang J et al. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation 121(9), 1113–1123 (2010).
  • Huang NF, Niiyama H, Peter C et al. Embryonic stem cell-derived endothelial cells engraft into the ischemic hindlimb and restore perfusion. Arterioscler. Thromb. Vasc. Biol. 30(5), 984–991 (2010).
  • Liang OD, Mitsialis SA, Chang MS et al. Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells 29(1), 99–107 (2011).
  • Umar S, de Visser YP, Steendijk P et al. Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension. Am. J. Physiol. Heart Circ. Physiol. 297(5), H1606–H1616 (2009).
  • Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science 282(5391), 1145–1147 (1998).
  • Green RM. Can we develop ethically universal embryonic stem-cell lines? Nat. Rev. Genet. 8(6), 480–485 (2007).
  • Baker DE, Harrison NJ, Maltby E et al. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat. Biotechnol. 25(2), 207–215 (2007).
  • Barrilleaux B, Phinney DG, Prockop DJ, O’Connor KC. Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng. 12(11), 3007–3019 (2006).
  • Lee RH, Kim B, Choi I et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell. Physiol. Biochem. 14(4-6), 311–324 (2004).
  • Zvaifler NJ, Marinova-Mutafchieva L, Adams G et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2(6), 477–488 (2000).
  • Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8(9), 726–736 (2008).
  • 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. 3(4), 393–403 (1970).
  • 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 17(4), 331–340 (1974).
  • Caplan AI. Mesenchymal stem cells. J. Orthop. Res. 9(5), 641–650 (1991).
  • Alhadlaq A, Mao JJ. Tissue-engineered neogenesis of human-shaped mandibular condyle from rat mesenchymal stem cells. J. Dent. Res. 82(12), 951–956 (2003).
  • Caplan AI. The mesengenic process. Clin. Plast. Surg. 21(3), 429–435 (1994).
  • Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18(12), 1417–1426 (1995).
  • 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 105(1), 93–98 (2002).
  • Kadivar M, Khatami S, Mortazavi Y, Shokrgozar MA, Taghikhani M, Soleimani M. in vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells. Biochem. Biophys. Res. Commun. 340(2), 639–647 (2006).
  • Rangappa S, Fen C, Lee EH, Bongso A, Sim EK, Wei EK. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann. Thorac. Surg. 75(3), 775–779 (2003).
  • Kode JA, Mukherjee S, Joglekar MV, Hardikar AA. Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy 11(4), 377–391 (2009).
  • Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4), 315–317 (2006).
  • Spencer ND, Gimble JM, Lopez MJ. Mesenchymal stromal cells: past, present, and future. Vet. Surg. 40(2), 129–139 (2011).
  • 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 103(5), 1662–1668 (2004).
  • Zuk PA, Zhu M, Ashjian P et al. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13(12), 4279–4295 (2002).
  • Huang S, Leung V, Peng S et al. Developmental definition of MSCs: new insights into pending questions. Cell. Reprogram. 13(6), 465–472 (2011).
  • Covas DT, Panepucci RA, Fontes AM et al. Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Exp. Hematol. 36(5), 642–654 (2008).
  • Halfon S, Abramov N, Grinblat B, Ginis I. Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev. 20(1), 53–66 (2011).
  • Chen Y, Shao JZ, Xiang LX, Dong XJ, Zhang GR. Mesenchymal stem cells: a promising candidate in regenerative medicine. Int. J. Biochem. Cell Biol. 40(5), 815–820 (2008).
  • Soncini M, Vertua E, Gibelli L et al. Isolation and characterization of mesenchymal cells from human fetal membranes. J. Tissue Eng. Regen. Med. 1(4), 296–305 (2007).
  • Battula VL, Treml S, Abele H, Bühring HJ. Prospective isolation and characterization of mesenchymal stem cells from human placenta using a frizzled-9-specific monoclonal antibody. Differentiation 76(4), 326–336 (2008).
  • Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. Circulating skeletal stem cells. J. Cell Biol. 153(5), 1133–1140 (2001).
  • Sabatini F, Petecchia L, Tavian M, Jodon de Villeroché V, Rossi GA, Brouty-Boyé D. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab. Invest. 85(8), 962–971 (2005).
  • Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22(4), 625–634 (2004).
  • Ichinose S, Muneta T, Koga H et al. Morphological differences during in vitro chondrogenesis of bone marrow-, synovium-MSCs, and chondrocytes. Lab. Invest. 90(2), 210–221 (2010).
  • Kögler G, Sensken S, Airey JA et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J. Exp. Med. 200(2), 123–135 (2004).
  • Young HE, Mancini ML, Wright RP et al. Mesenchymal stem cells reside within the connective tissues of many organs. Dev. Dyn. 202(2), 137–144 (1995).
  • Cheng MT, Yang HW, Chen TH, Lee OK. Isolation and characterization of multipotent stem cells from human cruciate ligaments. Cell Prolif. 42(4), 448–460 (2009).
  • Fu YS, Cheng YC, Lin MY et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24(1), 115–124 (2006).
  • Hida N, Nishiyama N, Miyoshi S et al. Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem Cells 26(7), 1695–1704 (2008).
  • Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant. 20(1), 5–14 (2011).
  • Jazedje T, Perin PM, Czeresnia CE et al. Human Fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures. J. Transl. Med. 7, 46 (2009).
  • Wang HS, Hung SC, Peng ST et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22(7), 1330–1337 (2004).
  • Crisostomo PR, Wang M, Wairiuko GM et al. High passage number of stem cells adversely affects stem cell activation and myocardial protection. Shock 26(6), 575–580 (2006).
  • Wagner W, Bork S, Horn P et al. Aging and replicative senescence have related effects on human stem and progenitor cells. PLoS ONE 4(6), e5846 (2009).
  • Heeschen C, Lehmann R, Honold J et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 109(13), 1615–1622 (2004).
  • Roobrouck VD, Ulloa-Montoya F, Verfaillie CM. Self-renewal and differentiation capacity of young and aged stem cells. Exp. Cell Res. 314(9), 1937–1944 (2008).
  • Zhang J, Lian Q, Zhu G et al. A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell 8(1), 31–45 (2011).
  • Lian Q, Lye E, Suan Yeo K et al. Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs. Stem Cells 25(2), 425–436 (2007).
  • Sze SK, de Kleijn DP, Lai RC et al. Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Mol. Cell Proteomics 6(10), 1680–1689 (2007).
  • Zhang J, Chan YC, Ho JC, Siu CW, Lian Q, Tse HF. Regulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-a-go-go 1 (hEAG1) potassium channel. Am. J. Physiol. Cell Physiol. 303(2), C115–C125 (2012).
  • Penn MS, Mangi AA. Genetic enhancement of stem cell engraftment, survival, and efficacy. Circ. Res. 102(12), 1471–1482 (2008).
  • Orlic D, Kajstura J, Chimenti S et al. Bone marrow cells regenerate infarcted myocardium. Nature 410(6829), 701–705 (2001).
  • Mangi AA, Noiseux N, Kong D et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat. Med. 9(9), 1195–1201 (2003).
  • Boomsma RA, Swaminathan PD, Geenen DL. Intravenously injected mesenchymal stem cells home to viable myocardium after coronary occlusion and preserve systolic function without altering infarct size. Int. J. Cardiol. 122(1), 17–28 (2007).
  • Huang W, Wang T, Zhang D et al. Mesenchymal stem cells overexpressing CXCR4 attenuate remodeling of postmyocardial infarction by releasing matrix metalloproteinase-9. Stem Cells Dev. 21(5), 778–789 (2012).
  • Tsuji H, Miyoshi S, Ikegami Y et al. Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes. Circ. Res. 106(10), 1613–1623 (2010).
  • Bagno LL, Werneck-de-Castro JP, Oliveira PF et al. Adipose-derived stromal cell therapy improves cardiac function after coronary occlusion in rats. Cell Transplant. 21(9), 1985–1996 (2012).
  • Le Visage C, Gournay O, Benguirat N et al. Mesenchymal stem cell delivery into rat infarcted myocardium using a porous polysaccharide-based scaffold: a quantitative comparison with endocardial injection. Tissue Eng. Part A 18(1–2), 35–44 (2012).
  • Latifpour M, Nematollahi-Mahani SN, Deilamy M et al. Improvement in cardiac function following transplantation of human umbilical cord matrix-derived mesenchymal cells. Cardiology 120(1), 9–18 (2011).
  • Tan MY, Zhi W, Wei RQ et al. Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits. Biomaterials 30(19), 3234–3240 (2009).
  • Hatzistergos KE, Quevedo H, Oskouei BN et al. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ. Res. 107(7), 913–922 (2010).
  • Quevedo HC, Hatzistergos KE, Oskouei BN et al. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc. Natl Acad. Sci. USA 106(33), 14022–14027 (2009).
  • Peng C, Yang K, Xiang P et al. Effect of transplantation with autologous bone marrow stem cells on acute myocardial infarction. Int. J. Cardiol. 162(3), 158–165 (2013).
  • Dixon JA, Spinale FG. Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ. Heart Fail. 2(3), 262–271 (2009).
  • Haghighi K, Kolokathis F, Pater L et al. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J. Clin. Invest. 111(6), 869–876 (2003).
  • Gandolfi F, Vanelli A, Pennarossa G, Rahaman M, Acocella F, Brevini TA. Large animal models for cardiac stem cell therapies. Theriogenology 75(8), 1416–1425 (2011).
  • Doevendans PA, Daemen MJ, de Muinck ED, Smits JF. Cardiovascular phenotyping in mice. Cardiovasc. Res. 39(1), 34–49 (1998).
  • Swynghedauw B. Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles. Physiol. Rev. 66(3), 710–771 (1986).
  • Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363(9411), 783–784 (2004).
  • Silva GV, Litovsky S, Assad JA et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111(2), 150–156 (2005).
  • Hamamoto H, Gorman JH 3rd, Ryan LP et al. Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. Ann. Thorac. Surg. 87(3), 794–801 (2009).
  • Hashemi SM, Ghods S, Kolodgie FD et al. A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction. Eur. Heart J. 29(2), 251–259 (2008).
  • Valina C, Pinkernell K, Song YH et al. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur. Heart J. 28(21), 2667–2677 (2007).
  • Chin SP, Poey AC, Wong CY et al. Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy. Cytotherapy 13(7), 814–821 (2011).
  • Hare JM, Traverse JH, Henry TD et al. 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. 54(24), 2277–2286 (2009).
  • Chen SL, Fang WW, Ye F et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am. J. Cardiol. 94(1), 92–95 (2004).
  • Williams AR, Trachtenberg B, Velazquez DL et al. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circ. Res. 108(7), 792–796 (2011).
  • Mohyeddin-Bonab M, Mohamad-Hassani MR, Alimoghaddam K et al. Autologous in vitro expanded mesenchymal stem cell therapy for human old myocardial infarction. Arch. Iran. Med. 10(4), 467–473 (2007).
  • Yang Z, Zhang F, Ma W et al. A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery. Cardiovasc. Ther. 28(6), 380–385 (2010).
  • Chen S, Liu Z, Tian N et al. Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J. Invasive Cardiol. 18(11), 552–556 (2006).
  • Chachques JC, Trainini JC, Lago N et al. Myocardial assistance by grafting a new bioartificial upgraded myocardium (MAGNUM clinical trial): one year follow-up. Cell Transplant. 16(9), 927–934 (2007).
  • Tse HF, Thambar S, Kwong YL et al. Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). Eur. Heart J. 28(24), 2998–3005 (2007).
  • Siu CW, Liao SY, Liu Y, Lian Q, Tse HF. Stem cells for myocardial repair. Thromb. Haemost. 104(1), 6–12 (2010).
  • Price MJ, Chou CC, Frantzen M et al. Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int. J. Cardiol. 111(2), 231–239 (2006).
  • Hou D, Youssef EA, Brinton TJ et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 112(Suppl. 9), I150–I156 (2005).
  • Kocher AA, Schuster MD, Szabolcs MJ et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med. 7(4), 430–436 (2001).
  • Suuronen EJ, Kuraitis D, Ruel M. Improving cell engraftment with tissue engineering. Semin. Thorac. Cardiovasc. Surg. 20(2), 110–114 (2008).
  • Haneef NL, Benadda S, Legrand F, Carpentier A, Chachques JC. Development of bioartificial myocardium by electrostimulation of 3D collagen scaffolds seeded with stem cells. Heart Int. 7(2), e14 (2012).
  • Psaltis PJ, Zannettino AC, Worthley SG, Gronthos S. Concise review: mesenchymal stromal cells: potential for cardiovascular repair. Stem Cells 26(9), 2201–2210 (2008).
  • Makkar RR, Price MJ, Lill M et al. Intramyocardial injection of allogenic bone marrow-derived mesenchymal stem cells without immunosuppression preserves cardiac function in a porcine model of myocardial infarction. J. Cardiovasc. Pharmacol. Ther. 10(4), 225–233 (2005).
  • Stamm C, Klose K, Choi YH. Clinical application of stem cells in the cardiovascular system. Adv. Biochem. Eng. Biotechnol. 123, 293–317 (2010).
  • Freyman T, Polin G, Osman H et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur. Heart J. 27(9), 1114–1122 (2006).
  • Dixon JA, Gorman RC, Stroud RE et al. Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction. Circulation 120(Suppl. 11), S220–S229 (2009).
  • Noiseux N, Gnecchi M, Lopez-Ilasaca M et al. Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol. Ther. 14(6), 840–850 (2006).
  • Acquistapace A, Bru T, Lesault PF et al. Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondria transfer. Stem Cells 29(5), 812–824 (2011).
  • Pijnappels DA, Schalij MJ, Ramkisoensing AA et al. Forced alignment of mesenchymal stem cells undergoing cardiomyogenic differentiation affects functional integration with cardiomyocyte cultures. Circ. Res. 103(2), 167–176 (2008).
  • Islam MN, Das SR, Emin MT et al. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat. Med. 18(5), 759–765 (2012).
  • Herrmann JL, Abarbanell AM, Weil BR et al. Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-alpha improves acute myocardial function. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299(1), R371–R378 (2010).
  • Timmers L, Lim SK, Arslan F et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res. 1(2), 129–137 (2007).
  • Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res. 103(11), 1204–1219 (2008).
  • Kinnaird T, Stabile E, Burnett MS et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109(12), 1543–1549 (2004).
  • Kinnaird T, Stabile E, Burnett MS et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ. Res. 94(5), 678–685 (2004).
  • Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ. Res. 109(8), 923–940 (2011).
  • Timmers L, Lim SK, Hoefer IE et al. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 6(3), 206–214 (2011).
  • Fidelis-de-Oliveira P, Werneck-de-Castro JP, Pinho-Ribeiro V et al. Soluble factors from multipotent mesenchymal stromal cells have antinecrotic effect on cardiomyocytes in vitro and improve cardiac function in infarcted rat hearts. Cell Transplant 21(5), 1011–1021 (2012).
  • Gnecchi M, He H, Noiseux N et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 20(6), 661–669 (2006).
  • Zuo S, Jones WK, Li H et al. Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injury. Stem Cells Dev. 21(4), 598–608 (2012).
  • Tang YL, Tang Y, Zhang YC, Qian K, Shen L, Phillips MI. Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J. Am. Coll. Cardiol. 46(7), 1339–1350 (2005).
  • Leri A, Kajstura J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration. Physiol. Rev. 85(4), 1373–1416 (2005).
  • 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. 4(Suppl. 1), S21–S26 (2007).
  • Lai VK, Ashraf M, Jiang S, Haider K. MicroRNA-143 is a critical regulator of cell cycle activity in stem cells with co-overexpression of Akt and angiopoietin-1 via transcriptional regulation of Erk5/cyclin D1 signaling. Cell Cycle 11(4), 767–777 (2012).
  • Xie C, Huang H, Sun X et al. MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4. Stem Cells Dev. 20(2), 205–210 (2011).
  • Cordes KR, Sheehy NT, White MP et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460(7256), 705–710 (2009).
  • Kim HW, Jiang S, Ashraf M, Haider KH. Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function. J. Mol. Med. 90(9), 997–1010 (2012).
  • Zhang LL, Liu JJ, Liu F et al. MiR-499 induces cardiac differentiation of rat mesenchymal stem cells through wnt/b-catenin signaling pathway. Biochem. Biophys. Res. Commun. 420(4), 875–881 (2012).
  • Wen Z, Zheng S, Zhou C, Yuan W, Wang J, Wang T. Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators. J. Cell. Mol. Med. 16(4), 657–671 (2012).
  • Simonneau G, Robbins IM, Beghetti M et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 54(Suppl. 1), S43–S54 (2009).
  • O’Callaghan DS, Savale L, Montani D et al. Treatment of pulmonary arterial hypertension with targeted therapies. Nat. Rev. Cardiol. 8(9), 526–538 (2011).
  • Barst RJ, Gibbs JS, Ghofrani HA et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54(Suppl. 1), S78–S84 (2009).
  • Lang G, Klepetko W. Lung transplantation for end-stage primary pulmonary hypertension. Ann. Transplant. 9(3), 25–32 (2004).
  • 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 114(Suppl. 1), I181–I185 (2006).
  • 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. 292(2), H1120–H1128 (2007).
  • Takemiya K, Kai H, Yasukawa H, Tahara N, Kato S, Imaizumi T. Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats. Basic Res. Cardiol. 105(3), 409–417 (2010).
  • Liu K, Liu R, Cao G, Sun H, Wang X, Wu S. Adipose-derived stromal cell autologous transplantation ameliorates pulmonary arterial hypertension induced by shunt flow in rat models. Stem Cells Dev. 20(6), 1001–1010 (2011).
  • 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 21(10), 2225–2239(2012).
  • Huh JW, Kim SY, Lee JH et al. Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am. J. Physiol. Lung Cell Mol. Physiol. 301(3), L255–L266 (2011).
  • Janssens SP, Thompson BT, Spence CR, Hales CA. Functional and structural changes with hypoxia in pulmonary circulation of spontaneously hypertensive rats. J. Appl. Physiol. 77(3), 1101–1107 (1994).
  • Patel KM, Crisostomo P, Lahm T et al. Mesenchymal stem cells attenuate hypoxic pulmonary vasoconstriction by a paracrine mechanism. J. Surg. Res. 143(2), 281–285 (2007).
  • Deng W, St Hilaire RC, Chattergoon NN, Jeter JR Jr, Kadowitz PJ. Inhibition of vascular smooth muscle cell proliferation in vitro by genetically engineered marrow stromal cells secreting calcitonin gene-related peptide. Life Sci. 78(16), 1830–1838 (2006).
  • Mercola M, Ruiz-Lozano P, Schneider MD. Cardiac muscle regeneration: lessons from development. Genes Dev. 25(4), 299–309 (2011).
  • Haider HKh. Bone marrow cells for cardiac regeneration and repair: current status and issues. Expert Rev. Cardiovasc. Ther. 4(4), 557–568 (2006).
  • Song H, Song BW, Cha MJ, Choi IG, Hwang KC. Modification of mesenchymal stem cells for cardiac regeneration. Expert Opin. Biol. Ther. 10(3), 309–319 (2010).
  • Afzal MR, Haider HKh, Idris NM, Jiang S, Ahmed RP, Ashraf M. Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-kappaB signaling. Antioxid. Redox Signal. 12(6), 693–702 (2010).
  • Jiang S, Haider HKh, Idris NM, Salim A, Ashraf M. Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ. Res. 99(7), 776–784 (2006).
  • Shujia J, Haider HK, Idris NM, Lu G, Ashraf M. Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. Cardiovasc. Res. 77(3), 525–533 (2008).
  • Lai VK, Afzal MR, Ashraf M, Jiang S, Haider HKH. Non-hypoxic stabilization of HIF-Ia during coordinated interaction between Akt and angiopoietin-1 enhances endothelial commitment of bone marrow stem cells. J. Mol. Med. 90(6), 719–730 (2012).
  • Simpson D, Liu H, Fan TH, Nerem R, Dudley SC Jr. A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling. Stem Cells 25(9), 2350–2357 (2007).
  • Simpson DL, Boyd NL, Kaushal S, Stice SL, Dudley SC Jr. Use of human embryonic stem cell derived-mesenchymal cells for cardiac repair. Biotechnol. Bioeng. 109(1), 274–283 (2012).
  • Shafy A, Fink T, Zachar V, Lila N, Carpentier A, Chachques JC. Development of cardiac support bioprostheses for ventricular restoration and myocardial regeneration. Eur. J. Cardiothorac. Surg. (2012) (Epub ahead of print).
  • Lushaj EB, Anstadt E, Haworth R et al. Mesenchymal stromal cells are present in the heart and promote growth of adult stem cells in vitro. Cytotherapy 13(4), 400–406 (2011).
  • Nakanishi C, Yamagishi M, Yamahara K et al. Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells. Biochem. Biophys. Res. Commun. 374(1), 11–16 (2008).
  • Zhang S, Sun A, Xu D et al. Impact of timing on efficacy and safetyof intracoronary autologous bone marrow stem cells transplantation in acute myocardial infarction: a pooled subgroup analysis of randomized controlled trials. Clin. Cardiol. 32(8), 458–466 (2009).
  • Bao C, Guo J, Lin G, Hu M, Hu Z. TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. Scand. Cardiovasc. J. 42(1), 56–62 (2008).
  • Mills WR, Mal N, Kiedrowski MJ et al. Stem cell therapy enhances electrical viability in myocardial infarction. J. Mol. Cell. Cardiol. 42(2), 304–314 (2007).
  • Wang D, Zhang F, Shen W et al. Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats. Int. J. Cardiol. 152(3), 314–320 (2011).
  • Wolf D, Reinhard A, Seckinger A, Gross L, Katus HA, Hansen A. Regenerative capacity of intravenous autologous, allogeneic and human mesenchymal stem cells in the infarcted pig myocardium-complicated by myocardial tumor formation. Scand. Cardiovasc. J. 43(1), 39–45 (2009).
  • Jeong JO, Han JW, Kim JM et al. Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ. Res. 108(11), 1340–1347 (2011).
  • Perin EC, Silva GV, Assad JA et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J. Mol. Cell. Cardiol. 44(3), 486–495 (2008).
  • Wang X, Jameel MN, Li Q et al. Stem cells for myocardial repair with use of a transarterial catheter. Circulation 120(Suppl. 11), S238–S246 (2009).
  • Meyer GP, Wollert KC, Lotz J et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration) trial. Circulation 113(10), 1287–1294 (2006).
  • Wollert KC, Meyer GP, Lotz J et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364(9429), 141–148 (2004).

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