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Mesenchymal Stem Cells for Cardiac Regenerative Therapy

  • Chapter
Bone Marrow-Derived Progenitors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 180))

Abstract

Until recently, the concept of treating the injured or failing heart by generating new functional myocardium was considered physiologically impossible. Major scientific strides in the past few years have challenged the concept that the heart is a post-mitotic organ, leading to the hypothesis that cardiac regeneration could be therapeutically achieved. Bone marrow-derived adult stem cells were among the first cell populations that were used to test this hypothesis. Animal studies and early clinical experience support the concept that therapeutically delivered mesenchymal stem cells (MSCs) safely improve heart function after an acute myocardial infarction (MI). MSCs produce a variety of cardio-protective signalling molecules, and have the ability to differentiate into both myocyte and vascular lineages. Additionally, MSCs are attractive as a cellular vehicle for gene delivery, cell transplantation or for tissue engineering because they offer several practical advantages. They can be obtained in relatively large numbers through standard clinical procedures, and they are easily expanded in culture. The multi-lineage potential of MSC, in combination with their immunoprivileged status, make MSCs a promising source for cell therapy in cardiac diseases. Here we provide an overview of biological characteristics of MSCs, experimental animal studies and early clinical trials with MSCs. In addition, we discuss the routes of cell delivery, cell tracking experiments and current knowledge of the mechanistic underpinnings of their action.

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References

  • Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110:3300–3305

    Article  PubMed  Google Scholar 

  • Agah R, Kirshenbaum LA, Abdellatif M, Truong LD, Chakraborty S, Michael LH, Schneider MD (1997) Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo. J Clin Invest 100:2722–2728

    PubMed  CAS  Google Scholar 

  • Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822

    Article  PubMed  CAS  Google Scholar 

  • Amado LC, Saliaris AP, Schuleri KH, St JM, Xie JS, Cattaneo S, Dur DJ, and Fitton T, Kuang JQ, Stewart G, Lehrke S, Baumgartner WW, Martin BJ, Heldman AW, Hare JM (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 102:11474–11479

    Article  PubMed  CAS  Google Scholar 

  • 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 (2006) Multi-modality non-invasive imaging demonstrates in-vivo cardiac regeneration following mesenchymal stem cell therapy. J Am Coll Cardiol 48:2116–2124

    Article  PubMed  Google Scholar 

  • American Heart Association (2006) Heart Disease and Stroke Statistics—2007 Update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2006) http://circ.ahajournals.org/cgi/content/short/CIRCULATION AHA.106.179918. Circulation. Published online ahead of print, 28 December 2006. Cited 16 January 2007

    Google Scholar 

  • Anversa P, Ricci R, Olivetti G (1986) Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. J Am Coll Cardiol 7:1140–1149

    Article  PubMed  CAS  Google Scholar 

  • Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882

    Article  PubMed  Google Scholar 

  • Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA, Leor J (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 108:863–868

    Article  PubMed  Google Scholar 

  • Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  PubMed  Google Scholar 

  • Becker AJ, McCulloch EA, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454

    Article  PubMed  CAS  Google Scholar 

  • Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 344:1750–1757

    Article  PubMed  CAS  Google Scholar 

  • 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 (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776

    Article  PubMed  CAS  Google Scholar 

  • Berry MF, Engler AJ, Woo YJ, Pirolli TJ, Bish LT, Jayasankar V, Morine KJ, Gardner TJ, Discher DE, Sweeney HL (2006) Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol 290:H2196–H2203

    Article  PubMed  CAS  Google Scholar 

  • Bindslev L, Haack-Sorensen M, Bisgaard K, Kragh L, Mortensen S, Hesse B, Kjaer A, Kastrup J (2006) Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation. Eur J Nucl Med Mol Imaging 33:1171–1177

    Article  PubMed  CAS  Google Scholar 

  • Boyle AJ, Schulman SP, Hare JM, Oettgen P (2006) Controversies in cardiovascular medicine: ready for the next step. Circulation 114:339–352

    Article  PubMed  Google Scholar 

  • Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650

    Article  PubMed  CAS  Google Scholar 

  • Chen SL, Fang WW, Qian J, Ye F, Liu YH, Shan SJ, Zhang JJ, Lin S, Liao LM, Zhao RC (2004a) Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction. Chin Med J (Engl) 117:1443–1448

    PubMed  Google Scholar 

  • Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, Zhang JJ, Chunhua RZ, Liao LM, Lin S, Sun JP (2004b) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 94:92–95

    Article  PubMed  Google Scholar 

  • Devine SM, Bartholomew AM, Mahmud N, Nelson M, Patil S, Hardy W, Sturgeon C, Hewett T, Chung T, Stock W, Sher D, Weissman S, Ferrer K, Mosca J, Deans R, Moseley A, Hoffman R (2001) Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Exp Hematol 29:244–255

    Article  PubMed  CAS  Google Scholar 

  • Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101:2999–3001

    Article  PubMed  CAS  Google Scholar 

  • Di NM, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    Article  Google Scholar 

  • Friedenstein AJ (1961) Osteogenetic activity of transplanted transitional epithelium. Acta Anat (Basel) 45:31–59

    PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    PubMed  CAS  Google Scholar 

  • Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA (2005) A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 48:1416–1423

    Article  PubMed  Google Scholar 

  • Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11:367–368

    Article  PubMed  CAS  Google Scholar 

  • Haynesworth SE, Goshima J, Goldberg VM, Caplan AI (1992) Characterization of cells with osteogenic potential from human marrow. Bone 13:81–88

    Article  PubMed  CAS  Google Scholar 

  • Haynesworth SE, Baber MA, Caplan AI (1996) Cytokine expression by human marrow derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 166:585–592

    Article  PubMed  CAS  Google Scholar 

  • Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109:625–637

    Article  PubMed  CAS  Google Scholar 

  • Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci U S A 99:8932–8937

    Article  PubMed  CAS  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002a) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49

    Article  PubMed  CAS  Google Scholar 

  • Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM (2002b) Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 30:896–904

    Article  PubMed  CAS  Google Scholar 

  • Katritsis DG, Sotiropoulou PA, Karvouni E, Karabinos I, Korovesis S, Perez SA, Voridis EM, Papamichail M (2005) Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv 65:321–329

    Article  PubMed  Google Scholar 

  • Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE (2004a) 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 94:678–685

    Article  PubMed  CAS  Google Scholar 

  • Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE (2004b) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109:1543–1549

    Article  PubMed  CAS  Google Scholar 

  • Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 18:307–316

    PubMed  CAS  Google Scholar 

  • Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30:215–222

    Article  PubMed  CAS  Google Scholar 

  • Kraitchman DL, Tatsumi M, Gilson WD, Ishimori T, Kedziorek D, Walczak P, Segars WP, Chen HH, Fritzges D, Izbudak I, Young RG, Marcelino M, Pittenger MF, Solaiyappan M, Boston RC, Tsui BM, Wahl RL, Bulte JW (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112:1451–1461

    Article  PubMed  Google Scholar 

  • Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, Mc-Carthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, Bacigalupo A (2005) Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 11:389–398

    Article  PubMed  Google Scholar 

  • Le BK, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441

    Article  Google Scholar 

  • Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev 85:1373–1416

    Article  PubMed  CAS  Google Scholar 

  • Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW(2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286

    Article  PubMed  CAS  Google Scholar 

  • Limana F, Germani A, Zacheo A, Kajstura J, Di CA, Borsellino G, Leoni O, Palumbo R, Battistini L, Rastaldo R, Muller S, Pompilio G, Anversa P, Bianchi ME, Capogrossi MC (2005) Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation. Circ Res 97:e73–e83

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Kitsis RN (1996) Induction of DNA synthesis and apoptosis in cardiac myocytes by E1A oncoprotein. J Cell Biol 133:325–334

    Article  PubMed  CAS  Google Scholar 

  • Ma J, Ge J, Zhang S, Sun A, Shen J, Chen L, Wang K, Zou Y (2005) Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction. Basic Res Cardiol 100:217–223

    Article  PubMed  CAS  Google Scholar 

  • Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL (1998) Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 176:57–66

    Article  PubMed  CAS  Google Scholar 

  • Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, Ogawa S (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:697–705

    Article  PubMed  CAS  Google Scholar 

  • Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, Dzau VJ (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9:1195–1201

    Article  PubMed  CAS  Google Scholar 

  • McCulloch EA, Till JE (1960) The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat Res 13:115–125

    Article  PubMed  CAS  Google Scholar 

  • Minguell JJ, Erices A, Conget P (2001) Mesenchymal stem cells. Exp Biol Med (Maywood) 226:507–520

    CAS  Google Scholar 

  • Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, Ishino K, Ishida H, Shimizu T, Kangawa K, Sano S, Okano T, Kitamura S, Mori H (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12:459–465

    Article  PubMed  CAS  Google Scholar 

  • Mouquet F, Pfister O, Jain M, Oikonomopoulos A, Ngoy S, Summer R, Fine A, Liao R (2005) Restoration of cardiac progenitor cells after myocardial infarction by self-proliferation and selective homing of bone marrow-derived stem cells. Circ Res 97:1090–1092

    Article  PubMed  CAS  Google Scholar 

  • Muraglia A, Cancedda R, Quarto R (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 113:1161–1166

    PubMed  CAS  Google Scholar 

  • Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, Yamagishi M, Mori H, Kangawa K, Kitamura S (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287:H2670–H2676

    Article  PubMed  CAS  Google Scholar 

  • Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 100:12313–12318

    Article  PubMed  CAS  Google Scholar 

  • Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lider O, Alon R, Zipori D, Lapidot T (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283:845–848

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Potapova I, Plotnikov A, Lu Z, Danilo P Jr, Valiunas V, Qu J, Doronin S, Zuckerman J, Shlapakova IN, Gao J, Pan Z, Herron AJ, Robinson RB, Brink PR, Rosen MR, Cohen IS (2004) Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res 94:952–959

    Article  PubMed  CAS  Google Scholar 

  • Price MJ, Chou CC, Frantzen M, Miyamoto T, Kar S, Lee S, Shah PK, Martin BJ, Lill M, Forrester JS, Chen PS, Makkar RR (2005) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol Oct 21

    Google Scholar 

  • Prockop DJ, Sekiya I, Colter DC (2001) Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3:393–396

    Article  PubMed  CAS  Google Scholar 

  • Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002) Chimerism of the transplanted heart. N Engl J Med 346:5–15

    Article  PubMed  Google Scholar 

  • Saito T, Kuang JQ, Bittira B, Al-Khaldi A, Chiu RC (2002) Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 74:19–24

    Article  PubMed  Google Scholar 

  • Schmidt A, Ladage D, Steingen C, Brixius K, Schinkothe T, Klinz FJ, Schwinger RH, Mehlhorn U, Bloch W (2006) Mesenchymal stem cells transmigrate over the endothelial barrier. Eur J Cell Biol July 3

    Google Scholar 

  • Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, Pittenger MF, Martin BJ (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73:1919–1925

    Article  PubMed  Google Scholar 

  • Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156

    Article  PubMed  CAS  Google Scholar 

  • Sissman NJ (1970) Developmental landmarks in cardiac morphogenesis: comparative chronology. Am J Cardiol 25:141–148

    Article  PubMed  CAS  Google Scholar 

  • Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, Yang YZ, Pan C, Ge J, Phillips MI (2004) Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117:3–10

    Article  PubMed  CAS  Google Scholar 

  • Tang YL, Tang Y, Zhang YC, Qian K, Shen L, Phillips MI (2005) Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol 46:1339–1350

    Article  PubMed  CAS  Google Scholar 

  • Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93–98

    Article  PubMed  Google Scholar 

  • Tomita S, Mickle DA, Weisel RD, Jia ZQ, Tumiati LC, Allidina Y, Liu P, Li RK (2002) Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg 123:1132–1140

    Article  PubMed  Google Scholar 

  • Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC (2003) Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75:389–397

    Article  PubMed  CAS  Google Scholar 

  • Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De AA, Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P (2005a) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673

    Article  PubMed  CAS  Google Scholar 

  • Urbanek K, Torella D, Sheikh F, De AA, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P (2005b) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 102:8692–8697

    Article  PubMed  CAS  Google Scholar 

  • Valiunas V, Doronin S, Valiuniene L, Potapova I, Zuckerman J, Walcott B, Robinson RB, Rosen MR, Brink PR, Cohen IS (2004) Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. J Physiol 555:617–626

    Article  PubMed  CAS  Google Scholar 

  • Vogel W, Grunebach F, Messam CA, Kanz L, Brugger W, Buhring HJ (2003) Heterogeneity among human bone marrow-derived mesenchymal stem cells and neural progenitor cells. Haematologica 88:126–133

    PubMed  Google Scholar 

  • von Harsdorf, Hauck L, Mehrhof F, Wegenka U, Cardoso MC, Dietz R (1999) E2F-1 over-expression in cardiomyocytes induces downregulation of p21CIP1 and p27KIP1 and release of active cyclin-dependent kinases in the presence of insulin-like growth factor I. Circ Res 85:128–136

    Google Scholar 

  • Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363:783–784

    Article  PubMed  Google Scholar 

  • Wilson EM, Moainie SL, Baskin JM, Lowry AS, Deschamps AM, Mukherjee R, Guy TS, St John-Sutton MG, Gorman JH III, Edmunds LH Jr, Gorman RC, Spinale FG (2003) Region and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation 107:2857–2863

    Article  PubMed  CAS  Google Scholar 

  • Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Xu Z, Xu Y, Cui G (2005a) Effects of mesenchymal stem cell transplantation on extracellular matrix after myocardial infarction in rats. Coron Artery Dis 16:245–255

    Article  PubMed  Google Scholar 

  • Xu X, Xu Z, Xu Y, Cui G (2005b) Selective down-regulation of extracellular matrix gene expression by bone marrow derived stem cell transplantation into infarcted myocardium. Circ J 69:1275–1283

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Zhou W, Zheng W, Ma Y, Lin L, Tang T, Liu J, Yu J, Zhou X, Hu J (2006) Effects of myocardial transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor for the improvement of heart function and angiogenesis after myocardial infarction. Cardiology 107:17–29

    Article  PubMed  Google Scholar 

  • Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, Hanley A, Scadova H, Qin G, Cha DH, Johnson KL, Aikawa R, Asahara T, Losordo DW (2005) Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 115:326–338

    Article  PubMed  CAS  Google Scholar 

  • Zhang S, Guo J, Zhang P, Liu Y, Jia Z, Ma K, Li W, Li L, Zhou C (2004) Long-term effects of bone marrow mononuclear cell transplantation on left ventricular function and remodeling in rats. Life Sci 74:2853–2864

    Article  PubMed  CAS  Google Scholar 

  • Zhang XY, La Russa VF, Bao L, Kolls J, Schwarzenberger P, Reiser J (2002) Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells. Mol Ther 5:555–565

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Miller School of Medicine, University of Miami and Johns Hopkins Medical Institutions, Stem Cell Institute and Cardiology Division, 1120 NW 14th Street, Miami, FL, 33136, USA

    K. H. Schuleri, A. J. Boyle & J. M. Hare

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  1. K. H. Schuleri
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  2. A. J. Boyle
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  3. J. M. Hare
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Correspondence to J. M. Hare .

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Editors and Affiliations

  1. Cardiovascular Disease Boehringer Ingelheim, Pharmaceuticals, Inc., 175 Briar Ridge Road, Ridgefield, CT, 06877, USA

    Katalin Kauser MD, PhD, DSc (Director) (Director)

  2. Department of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, D-60590, Frankfurt a. Main

    Andreas-Michael Zeiher MD (Professor Molecular Cardiology) (Professor Molecular Cardiology)

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Schuleri, K.H., Boyle, A.J., Hare, J.M. (2007). Mesenchymal Stem Cells for Cardiac Regenerative Therapy. In: Kauser, K., Zeiher, AM. (eds) Bone Marrow-Derived Progenitors. Handbook of Experimental Pharmacology, vol 180. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68976-8_9

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