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Thromb Haemost 2005; 94(04): 738-749
DOI: 10.1160/TH05-04-0233
Theme Issue Article
Schattauer GmbH

In search of the best candidate for regeneration of ischemic tissues

Are embryonic/fetal stem cells more advantageous than adult counterparts?
Costanza Emanueli
1   Experimental Cardiovascular Medicine, Bristol Heart Institute, University of Bristol, Bristol, UK
4   Molecular and Cellular Medicine, INBB Interuniversity Consortium, Osilo, Italy
,
Majlinda Lako
2   Centre for Stem Cell Biology and Developmental Genetics, University of Newcastle, Newcastle upon Tyne, UK
,
Miodrag Stojkovic
2   Centre for Stem Cell Biology and Developmental Genetics, University of Newcastle, Newcastle upon Tyne, UK
,
Paolo Madeddu
1   Experimental Cardiovascular Medicine, Bristol Heart Institute, University of Bristol, Bristol, UK
3   Experimental Medicine and Gene Therapy, Osilo, Italy
5   Multimedica Research Institute, Milan, Italy
› Author Affiliations
Further Information

Publication History

Received05 April 2005

Accepted after revision09 July 2005

Publication Date:
07 December 2017 (online)

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Summary

Human stem cells and progenitor cells from the bone marrow have been proposed for the regeneration of ischemic cardiac tissues. Early clinical trials indicate that infusion of autologous bone-marrow cells into the infarcted heart enhances ventricular function, albeit the long-term benefit remains to be ascertained. Alternatively, angiogenic growth factors could be used to stimulate the recruitment of vascular progenitor cells into tissues in need of regeneration. Unfortunately, in atherosclerotic patients, the curative potential of autologous stem cells might be impoverished by underlying disease and associated risk factors. Thus, research is focusing on the use of embryonic stem cells which are capable of unlimited self-renewal and have the potential to give rise to all tissue types in the body. Ethical problems and technical hurdles may limit the immediate application of embryonic stem cells. In the meanwhile, fetal hematopoietic stem cells, which have been routinely used to reconstitute the hematopoietic system in man, could represent an alternative, owing to their juvenile phenotype and ability to differentiate into vascular endothelial, muscular, and neuronal cell lineages. With progresses in stem cell expansion, the blood of a single cord could be sufficient to transplant an adult. These observations raise the exciting possibility of using fetal cells as a new way to speed up the healing of damaged tissues.

This study was partially supported by the Italian Health Institute (Stem Cell Program).

Keywords

Angiogenesis - vasculogenesis - ischaemic heart disease - fetal progenitor cells - nuclear transfer
 

  • References

  • 1 Poss KD, Wilson LG, Keating MT. Heart regeneration in zebrafish. Science 2002; 298: 2188-90.
    CrossrefPubMedGoogle Scholar
  • 2 Bettencourt-Dias M, Mittnacht S, Brockes JP. Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. J Cell Sci 2003; 116: 4001-9.
    CrossrefPubMedGoogle Scholar
  • 3 Asahara T, Murohara T, Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-7.
    CrossrefPubMedGoogle Scholar
  • 4 Asahara T, Takahashi T, Masuda H. et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 1999; 18: 3964-72.
    CrossrefPubMedGoogle Scholar
  • 5 Takahashi T, Kalka C, Masuda H. et al. Ischemiaand cytokine-induced mobilization of bone marrowderived endothelial progenitor cells for neovascularization. Nat Med 1999; 5: 434-8.
    CrossrefPubMedGoogle Scholar
  • 6 Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part II Cell-based therapy. Circulation 2004; 109: 2692-7.
    CrossrefPubMedGoogle Scholar
  • 7 Jackson KA, Majka SM, Wang H. et al. Regeneration of ischemic cardiac muscles and vascular endothelium by adult stem cells. J Clin Invest 2001; 107: 1395-402.
    CrossrefPubMedGoogle Scholar
  • 8 Orlic D, Kajstura J, Chimenti S. et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001; 410: 701-5.
    CrossrefPubMedGoogle Scholar
  • 9 Yoon YS, Wecker A, Heyd L. et al. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 2005; 115: 326-38.
    CrossrefPubMedGoogle Scholar
  • 10 Ferrari G, Cusella-De Angelis G, Coletta M. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279: 1528-30. Erratum Science 1998; 281: 923.
    CrossrefPubMedGoogle Scholar
  • 11 Lagasse E, Connors H, Al-Dhalimy M. et al. Purified hematopoietic stem cells can differentiate into hepatocytesin vivo . Nat Med 2000; 6: 1229-34.
    CrossrefPubMedGoogle Scholar
  • 12 Krause DS, Theise ND, Collector M I. et al. Multiorgan, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001; 105: 369-77.
    CrossrefPubMedGoogle Scholar
  • 13 Mezey E, Chandross KJ, Harta G. et al. Turning blood into brain: cells bearing neuronal antigens generatedin vivo from bone marrow. Science 2000; 290: 1779-82.
    CrossrefPubMedGoogle Scholar
  • 14 Beltrami AP, Barlucchi L, Torella D. et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-76.
    CrossrefPubMedGoogle Scholar
  • 15 Rehman J, Li J, Orschell C M. et al. Peripheral blood „endothelial progenitor cells” are derived from monocyte/ macrophages and secrete angiogenic growth factors. Circulation 2003; 107: 1164-9.
    CrossrefPubMedGoogle Scholar
  • 16 Peichev M, Naiyer AJ, Pereira D. et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000; 95: 952-8.
    CrossrefPubMedGoogle Scholar
  • 17 Goodell MA, Brose K, Paradis G. et al. Isolation and functional properties of murine hematopoietic stem cells that are replicatingin vivo . J Exp Med 1996; 183: 1797-806.
    CrossrefPubMedGoogle Scholar
  • 18 Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004; 95: 9-20.
    CrossrefPubMedGoogle Scholar
  • 19 Jiang Y, Jahagirdar BN, Reinhardt R L. et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-9.
    CrossrefPubMedGoogle Scholar
  • 20 Assmus B, Schachinger V, Teupe C. et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCAREAMI). Circulation 2002; 106: 3009-17.
    CrossrefPubMedGoogle Scholar
  • 21 Planat-Benard V, Menard C, Andre M. et al. Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 2004; 94: 223-9.
    CrossrefPubMedGoogle Scholar
  • 22 Taylor DA, Atkins BZ, Hungspreugs P. et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 1998; 4: 929-33.
    CrossrefPubMedGoogle Scholar
  • 23 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. 2004; 109: 1615-22
    CrossrefPubMedGoogle Scholar
  • 24 Vasa M, Fichtlscherer S, Aicher A. et al. 2001. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89: E1-E7
    PubMedGoogle Scholar
  • 25 Hill JM, Zalos G, Halcox J P. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348: 593-600.
    CrossrefPubMedGoogle Scholar
  • 26 Edelberg JM, Tang L, Hattori K. et al. Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res 2002; 90: E89-E93.
    CrossrefPubMedGoogle Scholar
  • 27 Torella D, Rota M, Nurzynska D. et al. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 2004; 94: 514-24.
    CrossrefPubMedGoogle Scholar
  • 28 Tateishi-Yuyama E, Matsubara H, Murohara T. et al. Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360: 427-35.
    CrossrefPubMedGoogle Scholar
  • 29 Strauer BE, Brehm M, Zeus T. et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106: 1913-8.
    CrossrefPubMedGoogle Scholar
  • 30 Wollert KC, Meyer GP, Lotz J. et al. Randomized controlled clinical trial of intracoronary autologous bone marrow cell transfer post myocardial infarction. Circulation 2003; 108: 2723.
    PubMedGoogle Scholar
  • 31 Kang HJ, Kim HS, Zhang S Y. et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 2004; 363: 751-6.
    CrossrefPubMedGoogle Scholar
  • 32 Kuethe F, Richartz BM, Sayer H G. et al. Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. Int J Cardiol 2004; 97: 123-7.
    CrossrefPubMedGoogle Scholar
  • 33 Menasche P, Hagege AA, Scorsin M. et al. Myoblast transplantation for heart failure. Lancet 2001; 357: 279-80.
    CrossrefPubMedGoogle Scholar
  • 34 Menasche P, Hagege AA, Vilquin J T. et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003; 41: 1078-83.
    CrossrefPubMedGoogle Scholar
  • 35 Perin EC, Dohmann HF, Borojevic R. et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003; 107: 2294-302.
    CrossrefPubMedGoogle Scholar
  • 36 Wojakowski W, Tendera M, Michalowska A. et al. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation 2004; 110: 3213-20.
    CrossrefPubMedGoogle Scholar
  • 37 Dawn B, Stein AB, Urbanek K. et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A 2005; 102: 3766-71.
    CrossrefPubMedGoogle Scholar
  • 38 Kajstura J, Rota M, Whang B. et al. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 2005; 96: 127-37.
    CrossrefPubMedGoogle Scholar
  • 39 Wang JS, Shum-Tim D, Chedrawy E. et al. The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications. J Thorac Cardiovasc Surg 2001; 122: 699-705.
    CrossrefPubMedGoogle Scholar
  • 40 Murry CE, Soonpaa MH, Reinecke H. et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004; 428: 664-8.
    CrossrefPubMedGoogle Scholar
  • 41 Balsam LB, Wagers AJ, Christensen J L. et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004; 428: 668-73.
    CrossrefPubMedGoogle Scholar
  • 42 Nygren JM, Jovinge S, Breitbach M. et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 2004; 10: 494-501.
    CrossrefPubMedGoogle Scholar
  • 43 Wagers AJ, Sherwood RI, Christensen JL. et al. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 297: 2256-9.
    CrossrefPubMedGoogle Scholar
  • 44 Terada N, Hamazaki T, Oka M. et al. Bone marrow cells adopt phenotype of other cells by spontaneous cell fusion. Nature 2002; 416: 542-5.
    CrossrefPubMedGoogle Scholar
  • 45 Fuchs S, Baffour R, Zhou Y F. et al. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol 2001; 37: 1726-32.
    CrossrefPubMedGoogle Scholar
  • 46 Kocher AA, Schuster MD, Szabolcs M J. et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7: 430-6.
    CrossrefPubMedGoogle Scholar
  • 47 Kinnaird T, Stabile E, Burnett M S. et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109: 1543-9.
    CrossrefPubMedGoogle Scholar
  • 48 Rafii S, Heissig B, Hattori K. Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors. Gene Ther 2002; 9: 631-41.
    CrossrefPubMedGoogle Scholar
  • 49 Pelosi E, Valtieri M, Coppola S. et al. Identification of the hemangioblast in postnatal life. Blood 2002; 100: 3203-8.
    CrossrefPubMedGoogle Scholar
  • 50 Iwaguro H, Yamaguchi J, Kalka C. et al. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 2002; 105: 732-8.
    CrossrefPubMedGoogle Scholar
  • 51 Kalka C, Tehrani H, Laudenberg B. et al. VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease. Ann Thorac Surg 2000; 70: 829-34.
    CrossrefPubMedGoogle Scholar
  • 52 Hattori K, Heissig B, Tashiro K. et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 2001; 97: 3354-60.
    CrossrefPubMedGoogle Scholar
  • 53 Hattori K, Heissig B, Wu Y. et al Placental growth factor reconstitutes hematopoiesis by recruiting vegfr1(+) stem cells from bone-marrow microenvironment. Nat Med 2002; 8: 841-9.
    CrossrefPubMedGoogle Scholar
  • 54 Heeschen C, Aicher A, Lehmann R. et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102: 1340-6.
    CrossrefPubMedGoogle Scholar
  • 55 Kermani P, Rafii D, Jin D K. et al. Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors. J Clin Invest 2005; 115: 653-63.
    CrossrefPubMedGoogle Scholar
  • 56 Heissig B, Hattori K, Dias S. et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002; 109: 625-37.
    CrossrefPubMedGoogle Scholar
  • 57 Matsubara H. Risk to the coronary arteries of intracoronary stem cell infusion and G-CSF cytokine therapy. Lancet 2004; 363: 746-7.
    CrossrefPubMedGoogle Scholar
  • 58 Dimmeler S, Aicher A, Vasa M. et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108: 391-7.
    CrossrefPubMedGoogle Scholar
  • 59 Iwakura A, Luedemann C, Shastry S. et al. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation 2003; 108: 3115-21.
    CrossrefPubMedGoogle Scholar
  • 60 Laufs U, Werner N, Link A. et al. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 2004; 109: 220-6.
    CrossrefPubMedGoogle Scholar
  • 61 Laugwitz KL, Moretti A, Lam J. et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 2005; 433: 647-53.
    CrossrefPubMedGoogle Scholar
  • 62 MacLellan WR, Garcia A, Oh H. et al. Overlapping roles of pocket proteins in the myocardium are unmasked by germline deletion of p130 plus heartspecific deletion of rb. Mol Cell Biol 2005; 25: 2486-97.
    CrossrefPubMedGoogle Scholar
  • 63 Jankowski M, Danalache B, Wang D. et al. Oxytocin in cardiac ontogeny. Proc Natl Acad Sci U S A 2004; 101: 13074-9.
    CrossrefPubMedGoogle Scholar
  • 64 Behfar A, Zingman LV, Hodgson D M. et al. Stem cell differentiation requires a paracrine pathway in the heart. FASEB J 2002; 16: 1558-66.
    CrossrefPubMedGoogle Scholar
  • 65 Oh H, Bradfute SB, Gallardo T D. et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 2003; 100: 12313-8.
    CrossrefPubMedGoogle Scholar
  • 66 Koyanagi M, Haendeler J, Badorff C. et al. Non-canonical Wnt signaling enhances differentiation of human circulating progenitor cells to cardiomyogenic cells. J Biol Chem. 2005 Feb 8; [Epub ahead of otherref.
    PubMedGoogle Scholar
  • 67 Messina E, De Angelis L, Frati G. et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 2004; 95: 911-21.
    CrossrefPubMedGoogle Scholar
  • 68 Stojkovic M, Lako L, Strachan T. et al. Derivation and characterisation of human embryonic stem cells. Reproduction 2004; 128: 259-67.
    CrossrefPubMedGoogle Scholar
  • 69 Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med 2003; 349: 275-86.
    CrossrefPubMedGoogle Scholar
  • 70 Hwang WS, Ryu YJ, Park J H. et al. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 2004; 303: 1669-74.
    CrossrefPubMedGoogle Scholar
  • 71 MacRae CA, Ellinor PT. Genetic screening and risk assessment in hypertrophic cardiomyopathy. Am Coll Cardiol 2004; 44: 2326-2328.
    CrossrefPubMedGoogle Scholar
  • 72 Hayashi T, Arimura T, Itoh-Satoh M. et al. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. J Am Coll Cardiol 2004; 44: 2192-201.
    CrossrefPubMedGoogle Scholar
  • 73 Voetsch B, Benke KS, Damasceno B P. et al. Siqueira LH Loscalzo. Paraoxonase 192 Gln–>Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke 2002; 33: 1459-464.
    CrossrefPubMedGoogle Scholar
  • 74 Lanza RP, Chung HY, Yoo J J. et al. Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol 2002; 20: 689-96.
    CrossrefPubMedGoogle Scholar
  • 75 Shiels PG, Kind AJ, Campbell K H. et al. Analysis of telomere lengths in cloned sheep. Nature 1999; 399: 316-7.
    CrossrefPubMedGoogle Scholar
  • 76 Lanza R, Cibelli JB, West MD. Human therapeutic cloning:. Nat Med 1999; 5: 975-7.
    CrossrefPubMedGoogle Scholar
  • 77 Lanza RP, Cibelli JB, West MD. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 2000; 288: 665-9.
    CrossrefPubMedGoogle Scholar
  • 78 Brodsky SV, Gealekman O, Chen J. et al. Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen. Circ Res 2004; 94: 377-84.
    CrossrefPubMedGoogle Scholar
  • 79 Lanza R, Moore MA, Wakayama T. et al. Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circ Res 2004; 94: 820-7.
    CrossrefPubMedGoogle Scholar
  • 80 Thomson JA, Itskovitz-Eldor J, Shapiro S S. et al. Embryonic stem cell line from human blastocysts. Science 1998; 282: 1145-7.
    CrossrefPubMedGoogle Scholar
  • 81 Reubinoff BE, Pera MF, Fong C Y. et al. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 2000; 18: 399-404.
    CrossrefPubMedGoogle Scholar
  • 82 Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cells. Stem Cell 2001; 19: 193-204.
    CrossrefPubMedGoogle Scholar
  • 83 Trounson A. Derivation characteristics and perspectives for mammalian pluripotential stem cells. Reprod Fertil Dev 2005; 17: 135-41.
    CrossrefPubMedGoogle Scholar
  • 84 Cowan CA, Klimanskaya I, McMahon J. et al. Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med 2004; 350: 1353-6.
    CrossrefPubMedGoogle Scholar
  • 85 Pickering SJ, Braude PR, Patel M. et al. Preimplantation genetic diagnosis as a novel source of embryos for stem cell research. RBM Online 2003; 7: 353-64.
    PubMedGoogle Scholar
  • 86 Stojkovic M, Lako M, Stojkovic P. et al. Derivation of human embryonic stem cells from Day 8 blastocysts recovered after three-step in vitro culture. Stem Cells 2004; 22: 790-7.
    CrossrefPubMedGoogle Scholar
  • 87 Strelchenko N, Verlinsky O, Kukharenko V. et al. Morula-derived human embryonic stem cells. Reprod Biomed Online 2004; 9: 623-9.
    CrossrefPubMedGoogle Scholar
  • 88 Martin MJ, Muotri A, Gage F. et al. Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med 2005; 11: 228-32.
    CrossrefPubMedGoogle Scholar
  • 89 Richards M, Fong CY, Chan W K. et al. Human feeders support prolonged undifferentiated growth of human inner cell masses and embryonic stem cell lines. Nat Biotechnol 2002; 20: 933-6.
    CrossrefPubMedGoogle Scholar
  • 90 Richards M, Fong CY, Chan W K. et al. An autogeneic feeder-system that efficiently supports undifferentiated growth of human embryonic stem cells. Stem Cells 2005; 23: 306-14.
    CrossrefPubMedGoogle Scholar
  • 91 Xu C, Inokuma MS, Denham J. et al. Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol 2001; 19: 971-4.
    CrossrefPubMedGoogle Scholar
  • 92 Rosler ES, Fisk GJ, Ares X. et al. Long-term culture of human embryonic stem cells in feeder-free conditions. Dev Dyn 2004; 229: 259-74.
    CrossrefPubMedGoogle Scholar
  • 93 Xu RH, Peck RM, Li DS. et al. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2005; 2: 185-90.
    CrossrefPubMedGoogle Scholar
  • 94 Klimanskaya I, Chung Y, Meisner L. et al. Human embryonic stem cells derived without feeder cells. The Lancet. http://thelancet.com/journal
    PubMedGoogle Scholar
  • 95 Zwaka TP, Thomson JA. Homologous recombination in human embryonic stem cells. Nat Biotechnol 2003; 21: 319-21.
    CrossrefPubMedGoogle Scholar
  • 96 Zaehres H, Lensch MW, Daheron L. et al. High-efficiency RNA interference in human embryonic stem cells. Stem Cells 2005; 23: 299-305.
    CrossrefPubMedGoogle Scholar
  • 97 Kim JH, Do HJ, Choi S J. et al. Efficient gene delivery in differentiated human embryonic stem cells. Exp Mol Med 2005; 37: 36-44.
    CrossrefPubMedGoogle Scholar
  • 98 Verlinsky Y, Strelchenko N, Kukharenko V. et al. Human embryonic stem cell lines with genetic disorders. Reprod Biomed Online 2005; 10: 105-10.
    CrossrefPubMedGoogle Scholar
  • 99 Vodyanik MA, Bork JA, Thomson J A. et al. Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood 2005; 105: 617-26
    CrossrefPubMedGoogle Scholar
  • 100 Gerecht-Nir S, Cohen S, Ziskind A. et al. Three-dimensional porous alginate scaffolds provide a conducive environment for generation of well-vascularized embryoid bodies from human embryonic stem cells. Biotechnol Bioeng 2004; 88: 313-20.
    CrossrefPubMedGoogle Scholar
  • 101 Wang L, Li L, Shojaei F. et al Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties. Immunity 2004; 21: 31-41.
    CrossrefPubMedGoogle Scholar
  • 102 Robin C, Ottersbach K, de Bruijn M. et al. Developmental origins of hematopoietic stem cells. Oncol Res 2003; 13: 315-21
    CrossrefPubMedGoogle Scholar
  • 103 Gerecht-Nir S, Dazard JE, Golan-Mashiach M. et al. Vascular gene expression and phenotypic correlation during differentiation of human embryonic stem cells. Dev Dyn 2005; 232: 487-97.
    CrossrefPubMedGoogle Scholar
  • 104 Klug MG, Soonpaa MH, Koh G Y. et al. Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest 1996; 98: 216-24.
    CrossrefPubMedGoogle Scholar
  • 105 Kehat I, Kenyagin-Karsenti D, Snir M. et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 2001; 108: 407-14.
    CrossrefPubMedGoogle Scholar
  • 106 Xu C, Police S, Rao N. et al. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 2002; 91: 501-8.
    CrossrefPubMedGoogle Scholar
  • 107 Muller M, Fleischmann BK, Selbert S. et al. Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB J 2000; 14: 2540-8.
    CrossrefPubMedGoogle Scholar
  • 108 David R, Groebner M, Franz WM. Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker. Stem Cells. 2005; 23: 477-82.
    CrossrefPubMedGoogle Scholar
  • 109 Nakahata T, Ogawa M. Hemopoietic colonyforming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors. J Clin Invest 1982; 70: 1324-8.
    CrossrefPubMedGoogle Scholar
  • 110 Grewal SS, Kahn JP, MacMillan ML. et al. Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis. Blood 2004; 103: 1147-51
    CrossrefPubMedGoogle Scholar
  • 111 Wagner JE, Kernan NA, Steinbuch M. et al. Allogeneic sibling umbilical cord blood transplantation in forty-four children with malignant and non-malignant disease. Lancet 1995; 46: 214-9.
    CrossrefPubMedGoogle Scholar
  • 112 Gluckman E, Rocha V, Boyer-Chammard A. et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997; 337: 373-81.
    CrossrefPubMedGoogle Scholar
  • 113 de La Selle V, Gluckman E, Bruley-Rosset M. Newborn blood can engraft adult mice without inducing graft-versus-host disease across non H-2 antigens. Blood 1996; 87: 3977-83.
    CrossrefPubMedGoogle Scholar
  • 114 Mayani H, Lansdorp PM. Thy-1 expression is linked to functional properties of primitive hematopoietic progenitor cells from human umbilical cord blood. Blood 1994; 83: 2410-7.
    CrossrefPubMedGoogle Scholar
  • 115 Vaziri H, Dragowska W, Allsopp R C. et al. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci USA 1994; 91: 9857-60.
    CrossrefPubMedGoogle Scholar
  • 116 Murohara T, Ikeda H, Duan J. et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 2000; 105: 1527-36.
    CrossrefPubMedGoogle Scholar
  • 117 Botta R, Gao E, Stassi G. et al. Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells. FASEB J 2004; 18: 1392-4.
    CrossrefPubMedGoogle Scholar
  • 118 Madeddu P, Emanueli C, Pelosi E. et al. Transplantation of low dose CD34+KDR+ cells promotes vascular and muscular regeneration in ischemic limbs. FASEB J 2004; 18: 1737-9.
    CrossrefPubMedGoogle Scholar
  • 119 Alessandri G, Girelli M, Taccagni G. et al. Human vasculogenesis ex vivo: embryonal aorta as a tool for isolation of endothelial cell progenitors. Lab Invest 2001; 81: 875-85.
    CrossrefPubMedGoogle Scholar
  • 120 Hoyer PE, Byskov AG, Mollgard K. Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries. Mol Cell Endocrinol 2005; 234: 1-10.
    CrossrefPubMedGoogle Scholar
  • 121 Zwaka TP, Thomson JA. A germ cell origin of embryonic stem cells?. Development 2005; 132: 227-33.
    CrossrefPubMedGoogle Scholar
  • 122 Liu S, Liu H, Pan Y. et al. Human embryonic germ cells isolation from early stages of post-implantation embryos. Cell Tissue Res 2004; 318: 525-31.
    CrossrefPubMedGoogle Scholar
  • 123 Sonntag KC, Simantov R, Isacson O. Stem cells may reshape the prospect. Mol Brain Res 2005; 134: 34-51.
    CrossrefPubMedGoogle Scholar
  • 124 Watanabe K, Nakamura M, Iwanami A. et al. Comparison between fetal spinal-cord- and forebrainderived neural stem/progenitor cells as a source of transplantation for spinal cord injury. Dev Neurosci 2004; 26: 275-87.
    CrossrefPubMedGoogle Scholar
  • 125 Mahieu-Caputo D, Allain JE, Branger J. et al. Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts. Hum Gene Ther 2004; 15: 1219-28.
    CrossrefPubMedGoogle Scholar
  • 126 Ottersbach K, Dzierzak E. The murine placenta contains hematopoietic stem cells within the vascular labyrinth region. Dev Cell 2005; 8: 377-87.
    CrossrefPubMedGoogle Scholar
  • 127 Gekas C, Dieterlen-Lievre F, Orkin S H. et al. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005; 8: 365-75.
    CrossrefPubMedGoogle Scholar
  • 128 Kibschull M, Nassiry M, Dunk C. et al. Connexin31- deficient trophoblast stem cells: a model to analyze the role of gap junction communication in mouse placental development. Dev Biol 2004; 273: 63-75.
    CrossrefPubMedGoogle Scholar
  • 129 Amoh Y, Li L, Katsuoka K. et al. Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proc Natl Acad Sci U S A 2005; 102: 5530-4.
    CrossrefPubMedGoogle Scholar
  • 130 Nishimura EK, Granter SR, Fisher DE. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 2005; 307: 720-4.
    CrossrefPubMedGoogle Scholar
  • 131 Jahoda CA, Whitehouse J, Reynolds A J. et al. Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages. Exp Dermatol 2003; 12: 849-59.
    CrossrefPubMedGoogle Scholar
  • 132 Budak MT, Alpdogan OS, Zhou M. et al. Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells. J Cell Sci 2005; 118: 1715-24.
    CrossrefPubMedGoogle Scholar
  • 133 Papini S, Rosellini A, Revoltella R P. et al. Selective growth and expansion of human corneal epithelial basal stem cells in a three-dimensional-organ culture. Differentiation 2005; 73: 61-8.
    CrossrefPubMedGoogle Scholar
  • 134 Pearton DJ, Yang Y, Dhouailly D. Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals. Proc Natl Acad Sci U S A 2005; 102: 3714-9.
    CrossrefPubMedGoogle Scholar
  • 135 Murrell W, Feron F, Wetzig A. et al. Multipotent stem cells from adult olfactory mucosa. Dev Dyn 2005; 233: 496-515.
    CrossrefPubMedGoogle Scholar
  • 136 Hahn CG, Han LY, Rawson N E. et al. In vivo and in vitro neurogenesis in human olfactory epithelium. J Comp Neurol 2005; 483: 154-63.
    CrossrefPubMedGoogle Scholar
  • 137 Rim JS, Mynatt RL, Gawronska-Kozak B. Mesenchymal stem cells from the outer ear: a novel adult stem cell model system for the study of adipogenesis. FASEB J. 2005; 19: 1205-7.
    CrossrefPubMedGoogle Scholar
  • 138 Gronthos S, Mankani M, Brahim J. et al. Post-natal dental pulp stem cellsin vivo and in vitro. Proc Natl Acad Sci U S A 2000; 97: 13625-30.
    CrossrefPubMedGoogle Scholar
  • 139 Komitova M, Mattsson B, Johansson B B. et al. Enriched environment Increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats. Stroke 2005; 36: 1278-82.
    CrossrefPubMedGoogle Scholar
  • 140 Sigurjonsson OE, Perreault MC, Egeland T. et al. Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. Proc Natl Acad Sci U S A 2005; 102: 5227-32.
    CrossrefPubMedGoogle Scholar
  • 141 Kondo T, Johnson SA, Yoder M C. et al. Sonic hedgehog and retinoic acid synergistically promote sensory fate specification from bone marrow-derived pluripotent stem cells. Proc Natl Acad Sci U S A 2005; 102: 4789-94.
    CrossrefPubMedGoogle Scholar
  • 142 Wislet-Gendebien S, Hans G, Leprince P. et al. Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 2005; 23: 392-402.
    CrossrefPubMedGoogle Scholar
  • 143 Long X, Olszewski M, Huang W. et al. Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells. Stem Cells Dev 2005; 14: 65-9.
    CrossrefPubMedGoogle Scholar
  • 144 Deasy BM, Gharaibeh BM, Pollett J B. et al. Longterm self-renewal of postnatal muscle-derived stem cells. Mol Biol Cell 2005; 16: 3323-33.
    CrossrefPubMedGoogle Scholar
  • 145 Payne TR, Oshima H, Sakai T. et al. Regeneration of dystrophin-expressing myocytes in the mdx heart by skeletal muscle stem cells. Gene Ther. 2005 April 21 [Epub ahead of print].
    PubMedGoogle Scholar
  • 146 Wang DW, Fermor B, Gimble J M. et al. Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells. J Cell Physiol 2005; 204: 184-91.
    CrossrefPubMedGoogle Scholar
  • 147 Ogawa R, Mizuno H, Watanabe A. et al. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice-including relationship of sex differences. Biochem Biophys Res Commun 2004; 319: 511-7.
    CrossrefPubMedGoogle Scholar
  • 148 Kuehn BM. Discovery boosts hope for heart repair. JAMA 2005; 293: 1434-5.
    CrossrefPubMedGoogle Scholar
  • 149 Smits AM, van Vliet P, Hassink R J. et al. The role of stem cells in cardiac regeneration. J Cell Mol Med 2005; 1: 25-36.
    CrossrefPubMedGoogle Scholar
  • 150 Lida M, Heike T, Yoshimoto M. et al. Identification of cardiac stem cells with FLK1, CD31, and VE-cadherin expression during embryonic stem cell differentiation. FASEB J 2005; 19: 371-8.
    CrossrefPubMedGoogle Scholar
  • 151 Clouston AD, Powell EE, Walsh M J. et al. Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis. Hepatology 2005; 41: 809-18.
    CrossrefPubMedGoogle Scholar
  • 152 Clark JB, Rice L, Sadiq T. et al. Hepatic progenitor cell resistance to TGF-beta1’s proliferative and apoptotic effects. Biochem Biophys Res Commun 2005; 329: 337-44.
    CrossrefPubMedGoogle Scholar
  • 153 Anglani F, Forino M, Del Prete D. et al. In search of adult renal stem cells. J Cell Mol Med 2004; 8: 474-87.
    CrossrefPubMedGoogle Scholar
  • 154 Bates CM, Lin F. Future strategies in the treatment of acute renal failure: growth factors, stem cells, and other novel therapies. Curr Opin Pediatr 2005; 17: 215-20.
    CrossrefPubMedGoogle Scholar
  • 155 Bussolati B, Bruno S, Grange C. et al. Isolation of renal progenitor cells from adult human kidney. Am J Pathol 2005; 166: 545-55.
    CrossrefPubMedGoogle Scholar
  • 156 Peters K, Panienka R, Li J. et al. Expression of stem cell markers and transcription factors during the remodeling of the rat pancreas after duct ligation. Virchows Arch 2005; 446: 56-63.
    CrossrefPubMedGoogle Scholar
  • 157 Trucco M. Regeneration of the pancreatic beta cell. J Clin Invest 2005; 115: 5-12.
    CrossrefPubMedGoogle Scholar